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Background: Hepatitis B is an important agent of liver disease in patients with chronic kidney disease and chronic HBV infection promotes the development of CKD in the adult general population. Patients with CKD have a suboptimal response to various vaccines, and it remains unclear how we boost the immune response of CKD patients to HB vaccine. Study aims and design: We performed a narrative review to assess the mechanisms of lower immunogenicity of HBV vaccine in CKD population; multiple approaches to improve the response rate of CKD patients to HBV vaccine have been reported. This is a very important topic for nephrologists who often serve as primary case providers for patients with CKD. Results: The recommended vaccine schedule for CKD patients including those on maintenance dialysis is based on recombinant vaccine, four doses (month 0,1,2, and 6; 40 mcg each) by intramuscular route (deltoid muscle). According to RCTs or observational studies, some recombinant vaccines with adjuvants (i.e., HBV-AS02 and HBV-AS04) look promising. HBV-AS04 showed to give better seroprotection rates and durable immune response over extended follow-ups compared with licensed HBV vaccine in CKD patients. The seroprotection rate was 95% (97/102) and 82% (202/248) in pre-dialysis and dialysis patients, respectively, one month after completing vaccine schedule with HBV-AS04. HBV-AS02 was superior to licensed vaccine in terms of seroprotection rate, 76.9% vs. 37.6%. Conclusions: We suggest adjuvanted recombinant (HBV-AS04) vaccine (0,1,2 and 3 months; 20 mcg each dose) and post vaccination testing of anti-HBs antibody after vaccination. Booster doses to patients whose anti-HBs titers fall below the seroprotection level (

The Latin American Association for the Study of the Liver (Asociación Latinoamericana para el Estudio del Hígado; ALEH) represents liver professionals in Latin America with the mission of promoting liver health and quality patient care by advancing the science and practice of hepatology and contributing to the development of a regional health policy framework. Fatty liver disease associated with metabolic dysfunction is of specific concern in the ALEH region, where its prevalence is one of the highest globally, second only to the Middle East. A recent consensus from an international panel recommended a new definition of fatty liver disease associated with metabolic dysfunction, including a shift in name from non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD), and adoption of a set of positive criteria to diagnose the disease, independent of alcohol intake or other liver diseases. Given, the importance of this proposal, ALEH invited leading members of regional nations to come to a consensus on it from a local perspective. We reached a consensus to endorse the proposal that the disease should be renamed as MAFLD and that the disease should be diagnosed by the proposed simple and easily applicable criteria. We expect that this change in nosology will result in improvements in disease awareness and in advances in scientific, economic, public health, political, and regulatory aspects of the disease.

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

The ongoing pandemic of coronavirus disease 2019 (COVID-19) pandemic poses a serious threat to healthcare systems globally. Information regarding how the infection affects the liver and relevance of pre-existing liver disease as a risk factor for acquiring the infection or having a severe disease are still scarce. Also, considerations in liver transplant patients, those having hepatocellular carcinoma or under immunosuppressive therapy are being matter of analysis as information is being generated. Different treatments for COVID-19 are currently under study, some of which may be associated to hepatotoxicity. In the present review we discuss current data on the COVID-19 and liver, aiming to provide hepatologists with updated information to face this pandemic. 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. Universidad Austral. Hospital Universitario Austral; Argentina Fil: Soza, Alejandro. Pontificia Universidad Católica de Chile; Chile

BACKGROUND AND AIMS:The advent of direct-acting antiviral agents promises to change the management of hepatitis C virus infection (HCV) in patients with chronic kidney disease (CKD), a patient group in which the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a 'real-world' cohort of patients with CKD.METHODS:We performed an observational single-arm multi-centre study in a large (n=198) cohort of patients with stage 1-3 CKD who underwent antiviral therapy with DAAs for the treatment of HCV. The primary end-point was sustained virologic response (serum HCV RNA

Background We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Patients and methods Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. Results We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. Conclusion Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH., Italian Ministry of University and Research (MIUR)-Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to clinic), A. Gerussi, L. Cristoferi, and P. Invernizzi acknowledge that this research was partially supported by the Italian Ministry of University and Research (MIUR)-Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to clinic).

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

Hepatitis C virus and chronic kidney disease are major public health issues all over the world and controversy persists regarding the role of Hepatitis C as a risk factor for the development of chronic kidney disease in the adult general population. Numerous studies found a relationship between positive anti-HCV antibody serologic prevalence and increased frequency of incidence, prevalence and accelerated progression of chronic kidney disease (CKD) over time. However, this has not been universally accepted. One method to analyze the relationship between anti-HCV status and CKD is to evaluate the impact of anti-HCV antiviral therapy on the risk of CKD in the general population. The availability of safe and effective drugs (direct-acting antiviral agents) for HCV eradication supports this approach. Novel data support the notion that sustained viral response with anti-HCV regimens leads to improvement of hepatic and extrahepatic outcomes. A systematic review with meta-analysis of clinical observational studies was recently performed on this point. Fifteen studies were retrieved (N.=356, 285 patients); a relationship between sustained viral response and lower rate of kidney disease was noted- the summary estimate for adjusted risk of kidney disease was 2.5 (95% CI: 1.41; 4.41) (P=0.0016). An association between anti-HCV therapy and reduced risk of kidney disease after comparison of treated vs. untreated cohorts was observed, the summary estimate for adjusted HR was 0.44 (95% CI: 0.25; 0.63) (P=0.0001). Several biologic mechanisms have been cited to explain the detrimental role of HCV on kidney disease in the general population, and a direct and indirect activity of HCV on atherogenesis at kidney level has been mentioned. Clinical and experimental studies are under way.

Introduction: Hepatitis B virus is an important cause of liver disease and has numerous extra-hepatic manifestations. HBV leads to important morbidity and mortality in the general population and recent evidence suggests a role of HBV in the incidence and progression of chronic kidney disease. Areas covered: The mechanisms underlying the link between HBV and CKD remain unclear. Nucleos(t)ide analogues for the antiviral treatment of HBV are currently available; these drugs are provided with high efficacy even in patients with CKD. Expert opinion: A recent meta-analysis of clinical studies showed that HBV results in a greater risk of CKD in the general population. According to an updated review (studies were identified from PubMed, EMBASE, and the Cochrane database), we retrieved six clinical studies (n = 1,034,773 unique patients), adjusted RR, 1.41 (95% CI, 1.09; 1.82, P < 0.001). The significant heterogeneity observed precluded more definitive conclusions. Various mechanisms have been cited to explain the greater risk of CKD among HBsAg positive carriers. Novel evidence shows that untreated HBV and therapy with nucleos(t)ide analogues are associated with increased and decreased risk of end-stage renal disease in CKD population, respectively. We recommend that patients with HBV are assessed for kidney function and urinary changes at baseline and over the follow-up.

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.

The massive implementation of the vaccine and antiviral agents against hepatitis B virus (HBV), targeting the envelope and viral polymerase genes, induces a selection pressure that might lead to the emergence of variants that impair the effectiveness of the vaccine, diagnostic methods and antiviral therapy. The aim of this study was to evaluate the prevalence of HBV vaccine escape mutants (VEMs), diagnostic failure mutants (DFMs) and treatment resistance mutants (ARMs) among individuals from Buenos Aires, Argentina. HBV surface antigen and polymerase sequences obtained from serum samples of 530 HBV-infected individuals were analysed. Samples belonged to genotypes A (28.1%), D (13.6%) and F (58.3%). VEMs, DMFs and ARMs were present in 40 (7.5%), 57 (10.7%) and 27 (5.1%) samples within the studied population. Additionally, eight nonpreviously reported VEMs and nine DFMs were identified. VEMs and DFMs were biased by genotype, being higher in genotype D (33.3% and 33.3%) compared to genotype A (6% and 17.4%) and genotype F (2.3% and 2.3%) (P > 0.001). On the contrary, there was no association between the presence of ARMs and HBV genotype (P = 0.324). VEMs, DFMs and ARMs create public health concerns. The current study provided valuable information about mutants in surface antigen and polymerase in HBV-infected patients from Argentina where HBV-F is the most prevalent genotype. Consequently, it constitutes an important reference for Latin American clinicians in order to optimize the management of HBV-infected patients. Fil: Di Lello, Federico Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; 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: Martínez, Alfredo P.. 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: Pérez, Paula Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Campos, Rodolfo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina Fil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina

Introduction and Objectives: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. Patients: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. Results: Overall, 4.6% (CI 3.7–5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14−25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P < .0001). Cirrhosis was independently associated with death [OR 3.1 (CI 1.9−4.8); P < .0001], adjusted by age, gender, and body mass index >30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). Conclusions: SARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIFC had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380. Fil: Mendizabal, Manuel. Universidad Austral; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina Fil: Ridruejo, Ezequiel. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Centro de Educación Médica e Investigaciones Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Piñero, Federico. Universidad Austral; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina Fil: Anders, Margarita. Hospital Alemán; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina Fil: Padilla, Martín Jesus. Hospital Nacional Guillermo Almenara Irigoyen; Perú Fil: Toro, Luis G.. Fundación de Medellín y Rionegro; Colombia Fil: Torre, Aldo. Instituto Nacional de Ciencias Médicas y Nutrición; México Fil: Montes, Pedro. Hospital Nacional Daniel A. Carrión; Argentina Fil: Urzúa, Alvaro. Universidad de Chile; Chile Fil: Gonzalez Ballerga, Esteban. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Silveyra, María Dolores. Sanatorio Anchorena; Argentina Fil: Michelato, Douglas. Hospital Especializado en Enfermedades Infecciosas Instituto Couto Maia; Brasil Fil: Díaz, Javier. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: Peralta, Mirta. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Pages, Josefina. Universidad Austral; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina Fil: García, Sandro Ruiz. Hospital de Víctor Lazarte Echegaray; Perú Fil: Gutierrez Lozano, Isabel. Centro Médico ABC; México Fil: Macias, Yuridia. IMSS Hospital General Regional No. 1 “Dr. Carlos Mc Gregor Sánchez”; México Fil: Cocozzella, Daniel. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Hospital Italiano de La Plata; Argentina Fil: Chavez Tapia, Norberto. Medica Sur Clinic & Foundation; México Fil: Tagle, Martín. Clínica Anglo-Americana; Perú Fil: Dominguez, Alejandra. Hospital Padre Hurtado; Chile Fil: Varón, Adriana. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Fundación Cardio Infantil; Colombia Fil: Vera Pozo, Emilia. Hospital Regional Dr. Teodoro Maldonado Carbo del IESS; Ecuador Fil: Higuera de la Tijera, Fátima. Hospital General de México “Dr. Eduardo Liceaga”; México Fil: Bustios, Carla. Fundación Cardio Infantil; Colombia Fil: Conte, Damián. Hospital Privado de Córdoba; Argentina Fil: Escajadillo, Nataly. Universidad Austral; Argentina Fil: Rubinstein, Fernando Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Especializado en Enfermedades Infecciosas Instituto Couto Maia; Brasil Fil: Tenorio, Laura. Hospital Nacional Edgardo Rebagliati Martins; Perú

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.

Background: data regarding outcome of Coronavirus disease 2019 (COVID-19) in patients with autoimmune hepatitis (AIH) are lacking. Patients and methods: we performed a retrospective study on AIH patients with COVID-19 from 34 centres in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity-score matched cohort of non-AIH patients with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase>2xupper limit of normal) during COVID-19 was also evaluated. Results: we included 110 AIH patients (80%,female) with a median age of 49 (range:18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (p=0.041; odds ratio (OR) 3.36[1.05-10.78]) while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (p=0.009; OR 0.26[0.09-0.71]). The rates of severe COVID-19 (15.5% vs 20.2% p=0.231) and all-cause mortality (10% vs 11.5%; p=0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (p, Italian Ministry of University; Research (MIUR)-Department of Excellence Project PREMIA; AMAF Monza ONLUS; AIRCS

Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) is an uncommon cause of liver disease presenting with a wide range of phenotypes and disease severity, acute hepatitis mimicking viral hepatitis to autoimmune hepatitis, steatosis, fibrosis or rare chronic vascular syndromes. Disease severity ranges from asymptomatic liver test abnormalities to acute liver failure. DILI has been traditionally classified in predictable or intrinsic (dose-related) or unpredictable (not dose-related) mechanisms. Few prospective studies are assessing the real prevalence and incidence of hepatotoxicity in the general population. DILI registries represent useful networks used for the study of liver toxicity, aimed at improving the understanding of causes, phenotypes, natural history, and standardized definitions of hepatotoxicity. Although most of the registries do not carry out population-based studies, they may provide important data related to the prevalence of DILI, and also may be useful to compare features from different countries. With the support of the Spanish Registry of Hepatotoxicity, our Latin American Registry (LATINDILI) was created in 2011, and more than 350 DILI patients have been recruited to date. This position paper describes the more frequent drugs and herbs-induced DILI in Latin America, mainly focusing on several features of responsible medicaments. Also, we highlighted the most critical points on the management of hepatotoxicity in general and those based on findings from our Latin American experience in particular.

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. Blood-borne infections are a major cause of harm in individuals on haemodialysis (HD). In particular, knowledge about hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency virus (HIV) status in HD patients is a major concern, since these infections may cause comorbidities in this setting. There is a paucity of data regarding this issue in Argentina. Hypothesis/Gap Statement. The epidemiological surveillance of HBV, HCV, and HIV is a fundamental tool for planning and implementing health strategies in order to prevent and control viral transmission of these viral agents. Aim. To determine the seroprevalence of HBV, HCV and HIV infections in HD patients in Buenos Aires, Argentina. Methodology. Seven hundred and forty-eight HD patients were included in a retrospective cross-sectional study. Serological assays were performed to determine HBV, HCV and HIV status. HBV HBsAg and anti-HBc IgG were analysed using AxSYM (samples before 2010) or the Architect Abbott system (samples since 2010), anti-HCV IgG testing was performed using the anti-HCV enzyme immunoassay AxSYM HCV V3.0 and ARCHITECT anti-HCV, while HIV was tested for using AxSYM HIV 1/2 gO and ARCHITECT HIV Ag/Ab Combination. HCV genotyping was carried out by phylogenetic analysis of the NS5B partial gene. Results. Infection with one of the viruses was detected in 31.1% of patients [HBV in 82 (11.0%), HCV in 179 (23.9%) and HIV in 6 (0.8%)]. Thirty-two (4.3%) patients had 2 virus markers [27 (3.6%) with HCV/HBV, 4 (0.5%) with HCV/HIV and 1 (0.13%) with HBV/HIV]. Finally, a single patient (0.13%) presented all three markers. Time on dialysis was correlated with HCV but not with HBV infection. The HCV subtype distribution in HD patients was inverted with respect to that observed in the general population (HCV-1a 73.2% and HCV-1b 26.8% in HD vs HCV-1a 26.5% and HCV-1b 73.5% in the general population, P

Background Herbal and dietary supplements (HDS) consumption, a growing cause of hepatotoxicity, is a common practice among Latin-American populations. Objectives: To evaluate clinical, laboratory features and outcome in HDS-hepatotoxicity included in the Latin America-Drug Induced Liver Injury (LATINDILI) Network. Methods A total of 29 adjudicated cases of HDS hepatotoxicity reported to the LATINDILI Network from October 2011 through December 2019 were compared with 322 DILI cases due to conventional drugs and 16 due to anabolic steroids as well as with other series of HDS-hepatotoxicity. Results From 367 DILI cases, 8% were attributed to HDS. An increasing trend in HDS-hepatotoxicity was noted over time (p = .04). Camellia sinensis, Herbalife® products, and Garcinia cambogia, mostly used for weight loss, were the most frequently adjudicated causative agents. Mean age was 45 years (66% female). Median time to onset was 31 days. Patients presented typically with hepatocellular injury (83%) and jaundice (66%). Five cases (17%) developed acute liver failure. Compared to conventional medications and anabolic steroids, HDS hepatotoxicity cases had the highest levels of aspartate and alanine transaminase (p = .008 and p = .021, respectively), had more re-exposure events to the culprit HDS (14% vs 3% vs 0%; p = .026), and had more severe and fatal/liver transplantation outcomes (21% vs 12% vs 13%; p = .005). Compared to other DILI cohorts, less HDS hepatotoxicity cases in Latin America were hospitalized (41%). Conclusions HDS-hepatotoxicity in Latin-America affects mainly young women, manifests mostly with hepatocellular injury and is associated with higher frequency of accidental re-exposure. HDS hepatotoxicity is more serious with a higher chance of death/liver transplantation than DILI related to conventional drugs.

Background and AimBlood-borne infections are a major cause of damage in individuals on hemodialysis (HD). In particular, knowledge about the viral status of hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency virus (HIV) in HD patients is gold data to face medical challenges. Related information is scarce in Argentina. The aim of this study was to determine the prevalence of HBV, HCV and HIV infections in HD patients from Buenos Aires, Argentina.MethodsSeven hundred and forty-eight HD patients were included in a retrospective cross-sectional study. Laboratories assays were performed to determine virological status. HCV genotyping was carried out by phylogenetic analysis of NS5B partial gene.ResultsInfection with one of the viruses was detected in 31.1% of patients [HBV in 82 (11.0%), HCV in 179 (23.9%), and HIV in 6 (0.8%)]. Thirty-two (4.3%) patients had two virus markers [27 (3.6%) with HCV/HBV, 4 (0.5%) with HCV/HIV and 1 (0.13%) with HBV/HIV]. Finally, one single patient (0.13%) presented all three markers. Time on dialysis was correlated with HCV infection but no with HBV. Distribution of HCV subtypes was inverted respect to the observed in general population [HCV-1a (73.2%) and HCV-1b (26.8%) in HD vs. HCV-1a (26.5%) and HCV-1b (73.5%) in general population, pConclusionsThese infections, mainly HCV, continue to occur at a very high rate in HD patients. Results emphasize the need to consider a priority the HCV infected patients in dialysis treatment and to vaccine against HBV in order to decrease its morbidity and mortality.

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

Background Argentina is considered a region of low seroprevalence of hepatitis E virus (HEV), however; no studies have evaluated its burden among acute hepatitis cases. Objectives: We aimed to estimate the proportion of acute HEV and outcome in a cohort of patients with acute hepatitis from 6 liver units in the Metropolitan area of Buenos Aires (MABA). Study design: We performed a prospective cohort study including patients ≥18 years with acute hepatitis (increase in transaminases x 5 ULN) fromJuly 2016 to May 2018. Severe hepatitis was defined as acute hepatitis + INR> 1.5 and acute liver failure as severe hepatitis + encephalopathy. In patients in whom other etiologies were excluded, HEV tests were performed: anti-HEV IgM/G and HEV-RNA in serum and feces. Results: Overall, 268 patients with acute hepatitis were included in the study. The most frequent etiologies of acute hepatitis were hepatitis B (67patients, 25 %), hepatotoxicity (65, 24 %) and autoimmune hepatitis (26, 10 %). Acute HEV infection was confirmed in 8 (2.98 %; 95 %CI 1.25–5.63) patients who tested positive for anti-HEV IgM. A total of 63 (23.5 %) patients were hospitalized and 9 (3.3 %) patients died. Overall, 48 (18 %) patients developed severe hepatitis, 6 (2.2 %) have acute liver failure, 6 (1.9 %) underwent liver transplantation and 9 (3.4 %) patients died. Conclusions: the proportion of acute HEV in MABA was low during the period studied. We believe our findings will aid physicians prioritize other etiologies of acute hepatitis over HEV in order to optimize diagnostic resources and offer better care to their patients

Latin America, a region with a population greater than 600000000 individuals, is well known due to its wide geographic, socio-cultural and economic heterogeneity. Access to health care remains as the main barrier that challenges routine screening, early diagnosis and proper treatment of hepatocellular carcinoma (HCC). Therefore, identification of population at risk, implementation of surveillance programs and access to curative treatments has been poorly obtained in the region. Different retrospective cohort studies from the region have shown flaws in the implementation process of routine surveillance and early HCC diagnosis. Furthermore, adherence to clinical practice guidelines recommendations assessed in two studies from Brazil and Argentina demonstrated that there is also room for improvement in this field, similarly than the one observed in Europe and the United States. In summary, Latin America shares difficulties in HCC decision-making processes similar to those from developed countries. However, a transversal limitation in the region is the poor access to health care with the consequent limitation to standard treatments for overall population. Specifically, universal health care access to the different World Health Organization levels is crucial, including improvement in research, education and continuous medical training in order to expand knowledge and generation of data promoting a continuous improvement in the care of HCC patients. Fil: Piñero, Federico. Educational And Awareness Network; Argentina. Hospital Universitario Austral; Argentina Fil: Poniachik, Jaime. Hospital Clinico de la Universidad de Chile; Chile. Clinica Santa Maria; Chile Fil: Ridruejo, Ezequiel. Hospital Universitario Austral; Argentina. Educational And Awareness Network; 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: Silva, Marcelo. Hospital Universitario Austral; Argentina. Educational And Awareness Network; Argentina

Fil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Medicas e Investigaciones Clinicas "Norberto Quirno". CEMIC-CONICET; Argentina. Hospital Universitario Austral; Argentina. Latin American Liver Research, Educational and Awareness Network; Argentina

Introduction: In 2011, the Latin-American DILI-Network (LATINDILIN) set up under the guidance of the Spanish DILI Registry a network of hepatologists to prospectively identify and characterize DILI patients. Aim: To evaluate the drugs more frequently associated with DILI in LA, clinical phenotype and outcome. Methods: Demographics, clinical and biochemical parameters of all cases included in the LATINDILI Network were analysed according to the type of liver injury (hepatocellular, Hep; cholestatic, Chol and mixed, Mix). Results: 404 DILI cases were included. Anti-infectives (31%), musculoskeletal system drugs (13%) and herbal products (9.2%) were the main causative therapeutic drug classes. Mean age was 49 years (female sex, 61%). Hep injury predominated (62%) whereas Chol and Mix patterns were 24% and 15% of cases, respectively. Chol patients (mean age 56y) were older than Hep and Mix cases (47 and 50, p

Incorporation of direct acting antivirals (DAA) in the treatment of Hepatitis C Virus (HCV) significantly increases sustained virologic response rates. However, despite the greater potency offered by these antivirals, drug resistance plays a key role in patients with failure to DAA. Nevertheless, there is no information about the prevalence of resistance-associated substitutions (RASs) in Argentina. The aim of this study was to analyze HCV variants resistant to protease inhibitors (PI) in naïve patients infected with HCV genotype 1 from Argentina. In this retrospective cross-sectional study, 103 patients infected with HCV-1 were included. Eighteen positions related with RASs were analyzed by Sanger at baseline and phylogenetic analysis was performed to determine the diversification of this samples. The analyzed RASs were present in 38 out of 103 patients (36.9%) infected with HCV-1. Patients infected with subtype HCV-1b had higher prevalence of baseline RASs than patients infected with HCV-1a [51.6% vs. 12.8%, respectively (p < 0.001)]. The Q80K polymorphism was not found in HCV-1a samples, even when 51% of them belonged to cluster 1, which is associated with a high frequency of Q80K. Phylogenetic analysis showed that Argentinean samples were intermingled with sequences from other geographic regions. RASs to PI were highly prevalent and subtype dependent in treatment-naïve Argentinean patients. Surprisingly, Q80K polymorphism was not detected in our study population. The phylogenetic analysis showed no relationship between our samples and other samples from Brazil which also present a low prevalence of Q80K. This study supports the need for surveillance of resistance in patients who will be treated with DAA in each particular country since the observed RASs have very different prevalence worldwide. Fil: Martínez, Alfredo P.. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina Fil: Culasso, Andrés Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Pérez, Paula Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Romano, Vanesa. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina Fil: Campos, Rodolfo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Ridruejo, Ezequiel. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina Fil: García, Gabriel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Di Lello, Federico Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina

We read with great interest the study of de Ledinghen et al regarding sustained virological rates (SVR) achieved in hepatitis C (HCV) patients with genotype (GT) 2 treated with sofosbuvir/daclatasvir regimen with or without ribavirin (SOF/DCV±R)1 . The authors reported lower SVR rates than expected in the HEPATHER cohort (88% and 91% in 12 and 24 weeks of treatment, respectively). Obesity and male sex were predictors associated with RVS failure and the authors suggested that SOF/DCV is "inherently insufficiently effective" in GT2 patients.

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 .

The ECHO model was developed to expand access to medical care for populations with HCV infection in underserved areas. We aimed to compare HCV treatment outcomes in community‐based clinics with the Austral University Hospital (AUH) and to assess improvement in physician knowledge and skills. In October 2015, we established an HCV ECHO clinic at the AUH in Buenos Aires. To evaluate the impact of this programme, we conducted a prospective cohort study comparing treatment for HCV infection at the AUH with healthcare providers from different Argentinean provinces. A survey evaluating skills and competence in HCV care was administered, and results were compared. The primary endpoint was sustained virologic response (SVR) and under direct‐acting antivirals. Since the implementation of ECHO clinics, a total of 25 physicians participated in at least one session (median 10.0; IQR 3.0‐18.0). SVR rates (n = 437 patients) were 94.2% (95% CI 90.4‐96.8) in patients treated at AUH clinic (n = 227/242) and 96.4% (95% CI 92.7‐98.5) in those treated at ECHO sites (n = 188/195), with a nonsignificant difference between sites, 2.2% SVR difference (95% CI −0.24‐0.06; P = 0.4). We also found a significant improvement in all the evaluated skills and abilities. Replicating the ECHO model helped to improve participants´ skills in the management of HCV achieving similar SVR rates. ECHO model was demonstrated to be an effective intervention able to multiply and expand HCV treatment, a critical barrier to access to care that needs to be solved if we are committed with WHO goals to eliminate HCV by 2030 Fil: Mendizabal, Manuel. Gobierno de la Provincia de Buenos Aires. Hospital Universitario Austral; Argentina Fil: Ridruejo, Ezequiel. Gobierno de la Provincia de Buenos Aires. Hospital Universitario Austral; Argentina Fil: Ceballos, Susana. Gobierno de la Provincia de Jujuy. Hospital San Roque; Argentina Fil: Sixto, Marcela. Gobierno de la Provincia de Santa Fe. Hospital José M. Cullen; Argentina Fil: Billordo, Ariel. Gobierno de la Provincia del Chaco. Hospital Julio C. Perrando; Argentina Fil: Gadea, Claudia. Sanatorio Pasquini de la Provincia de Tucumán; Argentina Fil: Mengarelli, Silvia. Gobierno de la Provincia de Cordoba. Nuevo Hospital San Roque.; Argentina Fil: Alonso, Cristina. Gobierno de la Provincia de Buenos Aires. Hospital Universitario Austral; Argentina Fil: Palazzo, Ana. Gobierno de la Provincia de Tucumán. Hospital Padilla; Argentina Fil: De María, Luis. Gobierno de la Provincia de Santa Fe. Hospital José M. Cullen; Argentina Fil: Bruno, Andrés. Gobierno de la Provincia de Buenos Aires. Hospital Argerich; Argentina Fil: Perez, Daniela. Gobierno de la Provincia de Tucumán. Hospital Padilla; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital Universitario Austral; Argentina Fil: Piñero, Federico. Gobierno de la Provincia de Buenos Aires. Hospital Universitario Austral; Argentina Fil: Deltrozzo, Verónica. Dual Medica de la Provincia de Santiago del Estero; Argentina Fil: Mendoza, Carlos. Gobierno de la Provincia de Río Cuarto. Hospital Central de Río Cuarto; Argentina Fil: Figueroa, Sebastián. Hospital Dr. Arturo Oñativia - Salta Capital.; Argentina Fil: Manero, Estela. Gobierno de la Provincia de Jujuy. Hospital Pablo Soria; Argentina Fil: Villa, Marina. Instituto Oulton de Córdoba; Argentina Fil: Barreyro, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina Fil: Moreno, Valeria. Gobierno de la Provincia de Cordoba. Nuevo Hospital San Roque.; Argentina Fil: Vilar, José. Asociación Argentina para el Estudio de las Enfermedades del Hígado; Argentina Fil: Murga, Dolores. Gobierno de la Provincia de Tucumán. Hospital Padilla; Argentina Fil: Fernandez, Marcelo. Gobierno de la Provincia de Entre Ríos. Hospital Bicentenario; Argentina Fil: O´Flaherty, Martin. University of Liverpool; Reino Unido Fil: Arora, Sanjeev. University of New Mexico; Estados Unidos Fil: Silva, Marcelo. Hospital Universitario Austral; Argentina

Real-world data evaluating the effectiveness of direct-acting antivirals (DAAs) in hepatitis C virus (HCV) treatment have been reported from different regions. Our aim was to evaluate the effectiveness and clinical outcomes of daclatasvir (DCV) and sofosbuvir (SOF) ± ribavirin (RBV) in a prospective multicentre cohort study including patients from Argentina and Brazil who received DCV/SOF ± RBV for 12 or 24 weeks from 2015 to 2018. Multivariable logistic regression models were carried out to identify factors associated with failure to achieve sustained virologic response (SVR) as a primary end point, and to death, decompensation, hepatocellular carcinoma (HCC) or liver transplantation (LT) as a composite secondary end point. From a total of 1517 patients treated with DCV/SOF, 906 completed 12 weeks post-treatment evaluation and were included in the analysis. Overall SVR12 rate was 96.1% (95% CI: 94.6%-97.2%), and 95% (95% CI: 92.8%-96.6%) in patients with cirrhosis. LT recipients and presence of cirrhosis were independently associated with failure to achieve SVR. During post-SVR12 follow-up, cumulative incidence of the secondary end point was 2.4% (95% CI: 1.5%-3.6%); two patients died from nonliver-related causes and two from HCC, five underwent LT, 12 developed HCC and 17 patients developed hepatic decompensation. Independent variables associated with these composite secondary end points were prior to HCV treatment and presence of cirrhosis. In conclusion, although the high pangenotypic effectiveness of DCV/SOF ± RBV was confirmed in our real-life cohort, patients with compensated and decompensated cirrhosis showed higher risk of non-SVR and complication appearance during treatment or after achieving SVR.

Introduction & objectives: The independent effect of liver biochemistries as a prognostic factor in patients with COVID-19 has not been completely addressed. We aimed to evaluate the prognostic value of abnormal liver tests on admission of hospitalized patients with COVID-19. Materials & methods: We performed a prospective cohort study including 1611 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through July 31, 2020 in 38 different Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters, including liver function tests, on admission and during hospitalization. All patients were followed until discharge or death. We fit multivariable logistic regression models, further post-estimation effect through margins and inverse probability weighting. Results: Overall, 57.8% of the patients were male with a mean age of 52.3 years, 8.5% had chronic liver disease and 3.4% had cirrhosis. Abnormal liver tests on admission were present on 45.2% (CI 42.7–47.7) of the cohort (n = 726). Overall, 15.1% (CI 13.4–16.9) of patients died (n = 244). Patients with abnormal liver tests on admission presented higher mortality 18.7% (CI 15.9–21.7), compared to those with normal liver biochemistries 12.2% (CI 10.1–14.6); P < .0001). After excluding patients with history of chronic liver disease, abnormal liver tests on admission were independently associated with death [OR 1.5 (CI 1.1–2.0); P = 0.01], and severe COVID-19 (2.6 [2.0–3.3], P < .0001), both adjusted by age, gender, diabetes, pneumonia and body mass index >30. Conclusions: The presence of abnormal liver tests on admission is independently associated with mortality and severe COVID-19 in hospitalized patients with COVID-19 infection and may be used as surrogate marker of inflammation. Fil: Mendizabal, Manuel. Universidad Austral. Hospital Universitario Austral; Argentina Fil: Piñero, Federico. Universidad Austral. Hospital Universitario Austral; 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: Anders, Margarita. Hospital Aleman; Argentina Fil: Silveyra, María Dolores. Sanatorio Anchorena; Argentina Fil: Torre, Aldo. Centro Médico ABC; México Fil: Montes, Pedro. Hospital Nacional Daniel A. Carrión; Perú Fil: Urzúa, Alvaro. Hospital Clínico de la Universidad de Chile; Chile Fil: Pages, Josefina. Universidad Austral. Hospital Universitario Austral; Argentina Fil: Toro, Luis G.. Hospitales de San Vicente Fundación de Medellín y Rionegro; Colombia Fil: Díaz, Javier. Hospital Nacional Edgardo Rebagliati Martins; Perú Fil: Gonzalez Ballerga, Esteban. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Miranda Zazueta, Godolfino. Instituto Nacional de Ciencias Médicas y Nutrición; México Fil: Peralta, Mirta. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Gutiérrez, Isabel. Centro Médico ABC; México Fil: Michelato, Douglas. Hospital Especializado en Enfermedades Infecciosas Instituto Couto Maia; Brasil Fil: Venturelli, Maria Grazia. Hospital Nacional Guillermo Almenara Irigoyen; Perú Fil: Varón, Adriana. Fundación Cardio-Infantil; Colombia Fil: Vera Pozo, Emilia. Hospital Regional Dr. Teodoro Maldonado Carbo; Ecuador Fil: Tagle, Martín. Clínica Anglo-Americana; Perú Fil: García, Matías. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina Fil: Tassara, Alfredo. Hospital Aleman; Argentina Fil: Brutti, Julia. Sanatorio Anchorena; Argentina Fil: Ruiz García, Sandro. Hospital de Víctor Lazarte Echegaray; Perú Fil: Bustios, Carla. Clínica Delgado; Perú Fil: Escajadillo, Nataly. Hospital Nacional Almanzor Aguinaga Asenjo; Perú Fil: Macias, Yuridia. No especifíca; Fil: Higuera de la Tijera, Fátima. Hospital General de México “Dr. Eduardo Liceaga"; México Fil: Gómez, Andrés J.. Hospital Universitario Fundación Santa Fé de Bogotá; Colombia Fil: Dominguez, Alejandra. Hospital Padre Hurtado; Chile Fil: Castillo Barradas, Mauricio. Hospital de Especialidades del Centro Médico Nacional La Raza; México Fil: Contreras, Fernando. No especifíca; Fil: Scarpin, Aldana. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina Fil: Schinoni, Maria Isabel. Hospital Alianza; Brasil Fil: Toledo, Claudio. Universidad Austral de Chile; Chile Fil: Girala, Marcos. Universidad Nacional de Asunción; Paraguay Fil: Mainardi, Victoria. Hospital Central De las Fuerzas Armadas; Uruguay Fil: Sanchez, Abel. Hospital Roosevelt; Guatemala Fil: Bessone, Fernando. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; Argentina Fil: Rubinstein, Fernando Adrian. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Silva, Marcelo Oscar. Universidad Austral. Hospital Universitario Austral; Argentina

There is scarce data pertaining to acute hepatitis C (aHC) infection in South America. We aimed to describe clinical characteristics and evolution of aHC in a South American cohort. A retrospective survey was conducted at 13 hepatology units. All patients ≥16 years old with aHC diagnosis were included. Demographic, clinical and outcome information were registered in a standardized ad hoc questionnaire. Sixty-four patients were included. The majority were middle-aged (median age: 46 years) and female (65.6%); most of them were symptomatic at diagnosis (79.6%). HCV-1 was the most prevalent genotype (69.2%). Five patients had liver failure: three cases of severe acute hepatitis, one case of fulminant hepatitis and one case of acute-on-chronic liver failure. Nosocomial exposure was the most prevalent risk factor. Evolution was assessed in 46 patients. In the untreated cohort, spontaneous resolution occurred in 45.8% and was associated with higher values of AST/ALT and with the absence of intermittent HCV RNA viremia (P = 0.01, 0.05, and 0.01, respectively). In the treated cohort, sustained virological response was associated with nosocomial transmission and early treatment initiation (P = 0.04 each). The prevalence of nosocomial transmission in this South-American cohort of aHC stresses the importance of following universal precautions to prevent HCV infection. J. Med. Virol. 89:276-283, 2017. © 2016 Wiley Periodicals, Inc.

Introduction: The selective inhibitors of COX-2, coxibs, are nonsteroidal anti-inflammatory drugs (NSAIDs) that have much better gastrointestinal safety profile as compared with non-selective NSAIDs. In this review, we analyze both the epidemiological features of coxib-induced hepatotoxicity and the clinical impact of coxib-associated liver damage, based on literature data. Areas covered: We carried out a search of the databases MEDLINE (PubMed), LILACS and SCIELO, from December 1999 to January 2016, to retrieve studies exploring the real impact of coxibs in liver toxicity as compared to non-selective COX-2 inhibitor NSAIDs. Expert opinion: Although reliable data on the incidence of celecoxib- and etoricoxib-induced hepatotoxicity are lacking, because of cohort studies have been generally underpowered to detect hepatic events, coxibs have been scarcely related to hepatotoxicity. Hence, coxib-induced liver injury seems to be an uncommon event, yet exhibits a wide spectrum of damage. Increasing COX-2 drug selectivity, as for rofecoxib, valdecoxib, parecoxib, and lumiracoxib, has been associated with higher cardiovascular risk, as well as dermatological and serious hepatic reactions. The actual risk of liver toxicity from the currently approved coxibs compared with non-selective NSAIDs will be discussed. Finally, classical and novel molecular mechanisms of coxib-induced hepatotoxicity are also described. Fil: Bessone, Fernando. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; Argentina Fil: Hernandez, Nelia. Universidad de la República; Uruguay 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: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Mendizabal, Manuel. Hospital Universitario Austral; Argentina Fil: Medina Cáliz, Inmaculada. Universidad de Málaga; España Fil: Robles Díaz, Mercedes. Universidad de Málaga; España Fil: Lucena, M. Isabel. Universidad de Málaga; España Fil: Andrade, Raúl J.. Universidad de Málaga; España

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.

Hepatitis C virus (HCV) screening according to the year of birth is recommended is some countries based on epidemiological data. The aim of this study was to analyze anti-HCV prevalence among people born between 1905 and 2015 in Argentina. Patients attending a tertiary care hospital in Buenos Aires, Argentina, from 2001 to 2015, who had a determination of anti-HCV, were included. Of 22,079 patients analyzed, 1,152 (5.2%; 95% confidence interval [CI]: 4.9%–5.5%) patients showed positive anti-HCV and 729 (3.3%; 95% CI: 3.1%–3.5%) patients showed detectable viremia. Three risk groups were identified (HCV prevalence): low-risk group—outpatient clinics/emergencies (2.8%); intermediate-risk group—in-patients (8%); and high-risk group—dialysis/transplants (27.2%). In the low-risk group, being born in 1973 or before was identified as a cut-off value for the risk of anti-HCV acquisition (area under the receiver-operator characteristic curve: 75.1 [95% asymptotic CI: 0.732–0.770; p

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

[Objective] To evaluate the use of hepatitis C virus (HCV) NS3 sequencing as alternative to the comercially available Versant HCV 2.0 reverse hybridization line-probe assay (LiPA 2.0) to determine HCV genotype 1 (HCV-1) subtypes., [Patients and methods] A cohort of 104 patients infected by HCV-1 according to LiPA 2.0 was analyzed in a cross-sectional study conducted in patients seen from January 2012 to June 2016 at an outpatient clinic in Buenos Aires, Argentina., [Results] The samples were included within well supported subtype clades: 64 with HCV-1b and 39 with HCV-1a infection. Twenty of the HCV-1a infected patientes were included in a supported sub-clade “1” and 19 individuals were among the basal sub-clade “2”. LiPA 2.0 failed to subtype HCV-1 in 20 (19.2%) individuals. Subtype classification determined by NS3 direct sequencing showed that 2/18 (11.1%) of the HCV-1a-infected patients as determined by LiPA 2.0 were in fact infected by HCV-1b. Of the HCV-1b-infected according to LiPA 2.0, 10/66 (15.2%) patients showed HCV-1a infection according to NS3 sequencing. Overall misclassification was 14.3% (κ-index for the concordance with NS3 sequencing = 0.635). One (1%) patient was erroneously genotyped as HCV-1 and was revealed as HCV genotype 4 infection., [Conclusions] Genomic sequencing of the HCV NS3 region represents an adequate alternative since it provides reliable genetic information. It even distinguishes between HCV-1a clades related to resistance-associated substitutions to HCV protease inhibitors, it provides reliable genetic information for genotyping/subgenotyping and simultaneously allows to determine the presence of resistance-associated substitutions to currently recommended DAAs., ACAC, and FAD are members of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) Research Career Program. KN is the recipient of a Miguel Servet research grant from the Instituto de Salud Carlos III (grant number CP13/00187). This work was supported by the Agencia Nacional de Investigaciones Científica y Técnicas (grant number PICT 2013-1268) and partially funded by the RD12/0017/0012 project as part of the Plan Nacional R+D+I and cofinanced by ISCIII-Subdirección General de Evaluación, the Fondo Europeo de Desarrollo Regional (FEDER).

WOS: 000426979400014, PubMed ID: 28404132, Background The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of-and expansion on-the 2014 analysis, which reported 80 million (95% CI 64-103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1.0% (95% uncertainty interval 0.8-1.1) in 2015, corresponding to 71.1 million (62.5-79.4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections., John C Martin Foundation, John C Martin Foundation.

Background. Bacterial infections are frequent complications in patients with cirrhosis. Since they are associated with poor outcomes, antibiotics are frequently over-prescribed. Surrogate markers of bacterial infections, like procalcitonin, are needed to better discriminate between infected and not infected patients. Aims. To evaluated the diagnostic accuracy of an ultra-sensitive procalcitonin assay for the diagnosis of bacterial infections in patients with cirrhosis. Material and methods. In a single-center prospective study, we determined the basal levels of procalcitonin in 106 episodes of admissions to the emergency department in 84 cirrhotic patients. Patients were classified as infected or not infected by two independent hepatologists blinded to the procalcitonin result. Results. The prevalence of bacterial infection was 28% (29 episodes). The median procalcitonin was significantly higher in the infected group than in the not infected group (0.45 vs. 0.061 ng/mL, p < 0.001). The diagnostic accuracy of procalcitonin for bacterial infection estimated by the ROC curve was 0.95 (CI: 95%, 0.91-0.99). When selecting a cutoff value of 0.098 ng/mL a sensitivity of 97% and a negative predictive value 98% were found. Conclusions. The use of an ultra-sensitive procalcitonin assay identifies patients with cirrhosis at very low risk of bacterial infections.

Combination therapy with pegylated interferon, ribavirin and the two first-generation NS3/4A protease inhibitors (PIs), telaprevir (TVR) and boceprevir (BOC), is the new standard-of-care therapy for patients who are chronically infected with genotype 1 hepatitis C virus. These combinations significantly increase sustained virological response (SVR) rates, but they also increase the rates of adverse events (AEs). Appearance of significant AEs may necessitate dose reduction or discontinuation of treatment, and may impact on virological response.In registration trials, IFN-related AEs were a dominant feature in both types of therapy. Some events were more frequent with PI-containing regimens, like anemia and dysgeusia with BOC and anemia, pruritus, rash and anorectal symptoms with TVR. This review addresses the early identification and management of AEs to improve tolerance, and to avoid reduction in SVR rates.Every patient will experience adverse effects to differing degrees; a systematic approach to their management can be very helpful. Early recognition and intervention can help clinicians ensure that patients are able to complete therapy where possible and achieve the goal of viral eradication. Treatment with the next generation of antivirals will improve safety and efficacy.

Glomerular disease is an extra-hepatic manifestation of hepatitis C virus infection (HCV) and membranoproliferative glomerulonephritis is the most frequent glomerular disease associated with HCV. It occurs commonly in patients with HCV-related mixed cryoglobulinemia syndrome. Patients with HCV-related glomerular disease have been historically a difficult-to-treat group. The therapeutic armamentarium for HCV-related glomerular disease now includes antiviral regimens, selective or non-specific immunosuppressive drugs, immunomodulators, and symptomatic agents. The treatment of HCV-associated glomerular disease is dependent on the clinical presentation of the patient. The recent introduction of all-oral, interferon (IFN)-free/ribavirin (RBV)-free regimens is dramatically changing the course of HCV in the general population, and some regimens have been approved for HCV even in patients with advanced chronic kidney disease. According to a systematic review of the medical literature, the evidence concerning the efficacy/safety of direct-acting antiviral agents (DAAs) of HCV-induced glomerular disease is limited. The frequency of sustained virological response was 92.5% (62/67). Full or partial clinical remission was demonstrated in many patients (n = 46, 68.5%) after DAAs. There were no reports of deterioration of kidney function in patients on DAAs. Many patients (n = 29, 43%) underwent immunosuppression while on DAAs. A few cases of new onset or relapsing glomerular disease in patients with HCV successfully treated with DAAs have been observed. In summary, DAA-based combinations are making easier the management of HCV. However, patients with HCV-induced glomerular disease are still a difficult-to-treat group even at the time of DAAs. Fil: Fabrizi, Fabrizio. No especifíca; Fil: Cerutti, Roberta. No especifíca; Fil: Porata, Giulia. No especifíca; Fil: Messa, Piergiorgio. Università degli Studi di Milano; Italia 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

Hepatitis C is a common cause of end-stage liver disease, and the main indication for liver transplantation in Latin America. Treatment of hepatitis C infected patients improves important long-term outcomes as mortality. Sustained viral response is reached in near 50% of patients with the previous management based in pegylated interferon and ribavirin. Recently new drugs were available increasing sustained viral response significantly, changing the standard of care to triple therapy. This guidelines provides a framework for practitioner in Latin America, to the management of patients with hepatitis C chronic infection.

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

AIM: To estimate the progression of the hepatitis C virus (HCV) epidemic and measure the burden of HCVrelated morbidity and mortality. METHODS: Age- and gender-defined cohorts were used to follow the viremic population in Argentina and estimate HCV incidence, prevalence, hepatic complications, and mortality. The relative impact of two scenarios on HCV-related outcomes was assessed: (1) increased sustained virologic response (SVR); and (2) increased SVR and treatment. RESULTS: Under scenario 1, SVR raised to 85%-95% in 2016. Compared to the base case scenario, there was a 0.3% reduction in prevalent cases and liverrelated deaths by 2030. Given low treatment rates, cases of hepatocellular carcinoma and decompensated cirrhosis decreased < 1%, in contrast to the base case in 2030. Under scenario 2, the same increases in SVR were modeled, with gradual increases in the annual diagnosed and treated populations. This scenario decreased prevalent infections 45%, liver-related deaths 55%, liver cancer cases 60%, and decompensated cirrhosis 55%, as compared to the base case by 2030. CONCLUSION: In Argentina, cases of end stage liver disease and liver-related deaths due to HCV are still growing, while its prevalence is decreasing. Increasing in SVR rates is not enough, and increasing in the number of patients diagnosed and candidates for treatment is needed to reduce the HCV disease burden. Based on this scenario, strategies to increase diagnosis and treatment uptake must be developed to reduce HCV burden in Argentina. Fil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Hospital Universitario Austral.; Argentina. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina Fil: Bessone, Fernando. Universidad Nacional de Rosario; Argentina Fil: Daruich, Jorge R.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Estes, Chris. Center For Disease Analysis; Estados Unidos Fil: Gadano, Adrián Carlos. Hospital Italiano; Argentina Fil: Razavi, Homie. Center For Disease Analysis; Estados Unidos Fil: Villamil, Federico. Hospital Británico de Buenos Aires; Argentina Fil: Silva, Marcelo Oscar. Universidad Austral. Hospital Universitario Austral.; Argentina

Currently, five nucleos(t)ide analogs (NAs) are approved for the treatment of chronic hepatitis B (CHB) infection. They are lamivudine, adefovir dipivoxil, telbivudine, entecavir (ETV) and tenofovir disoproxil fumarate (TDF). Two of them, ETV and TDF, are recommended as first-line treatment options. Their main advantages include excellent tolerability, antiviral potency and a high genetic barrier to resistance within medium duration treatment periods (2 - 6 years). In most patients, NAs need to be administered on a long-term basis. Several studies suggest that NAs long-term administration have been associated with low rates of serious adverse events (AEs), including lactic acidosis, renal function impairment, osteopenia and osteoporosis. Discontinuations due to AEs tended to be low in published randomized clinical trial and in the experience in clinical practice. NAs long-term use appears to be safe and effective; and in patients with advanced liver disease, despite preliminary concerning reports, their short-term use also appears to be safe and effective. Although major AEs are infrequent, they can be initially clinically silent yet lead to serious medical problems, therefore, a proactive surveillance and their prompt management is recommended.

BACKGROUND The prevalence of chronic hepatitis B virus (HBV) infection is high in patients with end-stage renal disease and in kidney transplant recipients, and there is little experience with treatment using the newer antiviral drugs. The aim of this study was to assess the efficacy and safety of entecavir in HBV infection in this difficult-to-treat population. METHODS Eleven male patients—1 with stage 4 chronic kidney disease, 7 undergoing hemodialysis, and 3 kidney transplant recipients-were included in the study evaluation. Six were treatment naive, and 5 were lamivudine resistant. Entecavir was administered at a dose of 0.1–1 mg qd according to the patients' renal function. All were HBsAg positive: 9 were HBeAg (+)/antiHBe (−), and the remaining 2 were HBeAg (−)/antiHBe (+). RESULTS After a median treatment of 2 ± 0.86 years, entecavir therapy was associated with a significant decrease in HBV DNA viral load: it was 6.84 ± 1.45 log10 UI/mL (range 5.21–9.04) at baseline and at the time of evaluation had dropped to 1.73 ± 2.11 log10 UI/mL (range

Introduction. Liver disease related to chronic viral hepatitis is a major cause of morbidity and mortality in renal transplant patients. There is no agreement upon the influence of chronic hepatitis B (HBV) and hepatitis C (HCV) infection in patient and graft survival.Aims. The aim of the study was to evaluate the influence of HBV and HCV on patient and graft short and long term survival, in the patients transplanted at our institution.Materials and methods. We evaluated the influence of antiHCV and HBsAg status (positive vs. negative); sex; age (> 49 years vs. < 49 years at transplantation); time on dialysis (> 3 vs. < 3 years); acute rejection; kind of graft (deceased vs. living donor, and kidney versus kidney and pancreas); number of transplantations; use of induction immunosuppression; and maintenance immunosuppression treatment (comparing the traditional triple therapy containing azathioprine, cyclosporine and prednisone vs. newer regimens which include tacrolimus, mycophenolate mofetil, sirolimus, etc) on the survival, long term and within the first month of transplantation, of the graft and the patients transplanted in our Institution between January 1991 and August 2009.Results. We included 542 patients, 60% males’ median age of 42.03 years (SD 13.06 years). 180 patients (33%) were antiHCV positive and 23 (4%) were HBsAg positive. AntiHCV positive, traditional triple therapy and acute rejection were associated with diminished graft survival. Older age, antiHCV positive, HBsAg positive, deceased donor, kidney-pancreas transplantation and traditional triple therapy were associated with diminished patient survival. Traditional triple therapy was associated with diminished one month graft survival; and older age and antiHCV positive were associated with diminished one month patient survival.Conclusion. In our experience, antiHCV positive status was associated with diminished long term patient and graft survival, and diminished six month graft survival; and HBsAg positive was associated with diminished patient survival.