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© 2022 American Association for the Study of Liver Diseases.Background and Aims: A few case reports of autoimmune hepatitis–like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series. Approach and Results: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18–79) years at presentation. Liver injury was diagnosed a median 15 (range: 3–65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3–4 liver injury than for grade 1–2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up. Conclusions: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.

The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions (RAS). However, the consequence of resistance selection during new direct-acting antiviral drug (DAA) treatment is not necessarily the therapeutic failure. In fact, DAA treatment has shown a high rate (> 95%) of sustained virological response even when high baseline RAS prevalence has been reported. In the context of RAS emergence and high rates of sustained viral response, the clinical relevance of variants harboring RAS is still controversial. Therefore, in order to summarize the data available in international guidelines, we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.

To achieve WHO's goal of eliminating hepatitis C virus (HCV), innovative strategies must be designed to diagnose and treat more patients. Therefore, we aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to HCV care. We conducted an implementation study utilizing a strategy to contact patients with HCV who were not under regular follow-up in 13 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or equivalent. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined by anti-HCV+ and detectable HCV-RNA. Identified patients who were not under follow-up by a liver specialist were contacted by telephone or email, and offered a medical reevaluation. A total of 10,364 patients were classified to have HCV. After reviewing their medical charts, 1349 (13%) had undetectable HCV-RNA or were wrongly coded. Overall, 9015 (86.9%) individuals were identified with chronic HCV infection. A total of 5096 (56.5%) patients were under routine HCV care and 3919 (43.5%) had been LTFU. We were able to contact 1617 (41.3%) of the 3919 patients who were LTFU at the primary medical institution, of which 427 (26.4%) were cured at a different institutions or were dead. Of the remaining patients, 906 (76.1%) were candidates for retrieval. In our cohort, about one out of four patients with chronic HCV who were LTFU were candidates to receive treatment. This strategy has the potential to be effective, accessible and significantly impacts on the HCV care cascade.

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 Choosing Wisely (CW) initiative aims to improve daily practice supported by evidence concerning unnecessary medical tests, procedures, and treatments. This philosophy is essential in managing viral hepatitis (VH), which primary care physicians increasingly carry out. It is also essential to achieving disease elimination. Thus, the aim of our study was to propose evidence-based CW recommendations in VH.The Brazilian Society of Hepatology (SBH) formed a panel of experts in VH who selected evidence-based CW recommendations, which were subsequently scrutinized and ranked by all members of SBH using a web-based approach.Five recommendations were chosen in order of importance: 1) do not order anti-HCV testing after achieving sustained virological response; 2) do not request serial HCV viral load to evaluate HCV progression, 3) do not add ribavirin to direct-acting antivirals in non-cirrhotic, naïve HCV patients; 4) do not screen for hepatocellular carcinoma in HCV patients with none to moderate fibrosis (≤ F2); 5) do not request anti-HBs after HBV vaccination, except for children born to HBV-infected mothers, hemodialysis patients, healthcare professionals, people who have had sexual contact with chronic HBV carriers, HIV-positive persons and immunocompromised individuals (hematopoietic stem-cell transplant recipients or persons receiving chemotherapy).CW recommendations may help general practitioners adopt a more rational and cost-effective approach in managing patients with VH in Brazil and Latin America, leading to lesser waste or harm to patients.

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

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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

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.

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.

[Introduction and alm]: Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins, may reduce the incidence of various tumors, including HCC. Antitumoral activities may be mediated by changes in transforming growth factor-beta (TGF-βΙ) and thyroid hormones (TH) regulation. Aim. The aim of our study is to establish the statins mechanism of action and the potential key molecules involved in an in vivo and in vitro HCC model., [Materials and methods]: We used two models: in vivo (in rats) using diethylnitrosamine (DEN) and hexachlorobenzene (HCB) to develop HCC. We analyzed cell proliferation parameters (proliferating cell nuclear antigen, PCNA) and cholesterol metabolism (hydroxy-methylglutaryl-CoA reductase, HMGCoAR). In vitro (Hep-G2 cells) we evaluated the effects of different doses of Atorvastatin (AT) and Simvastatin (SM) on HCB induced proliferation and analyzed proliferative parameters, cholesterol metabolism, TGF-βΙ mRNA, c-Src and TH levels., [Results]: In vivo, we observed that cell proliferation significantly increased as well as cholesterol serum levels in rats treated with HCB. In vitro, we observed the same results on PCNA as in vivo. The statins prevented the increase in HMG-CoAR mRNA levels induced by HCB, reaching levels similar to controls at maximum doses: AT (30 μM), and SM (20 μM). Increases in PCNA, TGF-βΙ, and pc-Src, and decreases in deiodinase I mRNA levels induced by HCB were not observed when cells were pre-treated with AT and SM at maximum doses., [Conclusion]: Statins can prevent the proliferative HCB effects on Hep-G2 cells. TGF-βΙ, c-Src and TH may be the statins molecular targets in hepatocarcinogenesis., This work was supported by grant SAF2012-32491 from Plan Nacional (MINECO) and grant S2010/BDM-2423 (MOIR) from Comunidad de Madrid, Spain, and by a grant UBACYT 20020120200258 /EXP-UBA N° 17064/ 2012 from Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, 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

Introduction and Objectives: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the impact of SARS-CoV-2 infection on clinical 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 compared to 16% in those without cirrhosis (P30. 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

Background & Aims: HBV infection exhibits geographical variation in its distribution in South America. While HBV rates are low in central Argentina, the north-western region exhibits intermediate HBV rates. Unfortunately, the reasons that could explain this difference are still unknown. Methods: a total of 1440 Argentines were recruited and grouped into HBV patients, HBV-resolved individuals and healthy controls. Genetic ancestry was assessed by analysis of biparental lineages and ancestry autosomal typing. SNPs of HLA-DPA1 (rs3077), HLA-DPB1 (rs9277542), HLA-DQB1 (rs2856718) and HLA-DQB2 (rs7453920) were determined, and HBV genotyping was performed by phylogenetic analysis in HBV patients. Results: Native American ancestry prevailed in the north-western region when compared with central Argentina (P

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 .

Fil: Ridruejo, Ezequiel. Educational And Awareness Network; Argentina. Centro de Educacion Medica e Investigaciones Clinicas "Norberto Quirno"; Argentina. Universidad Austral. Hospital Universitario Austral; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina

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

Hepatitis C virus (HCV) infection is a global health concern with an estimated worldwide disease prevalence rate of 1%, meaning 71 million individuals are infected.1 In the United States, the estimated prevalence rate is 0.7%, or 7 million individuals.1 Specifically in Latin America, estimations suggest that only 25% of individuals with suspected HCV infection have been diagnosed, and only 4% received treatment.2 Recent availability in this region of directacting antivirals (DAAs), which are safer and more effective than the interferon-based therapies, may influence treatment paradigms at country levels. Fil: Ridruejo, Ezequiel. Hospital Universitario Austral; Argentina. Latin American Liver Research, Educational and Awareness Network; Argentina. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Soza, Alejandro M. D.. Pontificia Universidad Católica de Chile; Chile

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.

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.

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

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.

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

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.

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

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.

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