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Introduction and Objectives: Autoimmune liver diseases (AILDs) are rare and require precise evaluation, which is often challenging for medical providers. Chatbots are innovative solutions to assist healthcare professionals in clinical management. In our study, ten liver specialists systematically evaluated four chatbots to determine their utility as clinical decision support tools in the field of AILDs. Materials and Methods: We constructed a 56-question questionnaire focusing on AILD evaluation, diagnosis, and management of Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), and Primary Sclerosing Cholangitis (PSC). Four chatbots -ChatGPT 3.5, Claude, Microsoft Copilot, and Google Bard- were presented with the questions in their free tiers in December 2023. Responses underwent critical evaluation by ten liver specialists using a standardized 1 to 10 Likert scale. The analysis included mean scores, the number of highest-rated replies, and the identification of common shortcomings in chatbots performance. Results: Among the assessed chatbots, specialists rated Claude highest with a mean score of 7.37 (SD = 1.91), followed by ChatGPT (7.17, SD = 1.89), Microsoft Copilot (6.63, SD = 2.10), and Google Bard (6.52, SD = 2.27). Claude also excelled with 27 best-rated replies, outperforming ChatGPT (20), while Microsoft Copilot and Google Bard lagged with only 6 and 9, respectively. Common deficiencies included listing details over specific advice, limited dosing options, inaccuracies for pregnant patients, insufficient recent data, over-reliance on CT and MRI imaging, and inadequate discussion regarding off-label use and fibrates in PBC treatment. Notably, internet access for Microsoft Copilot and Google Bard did not enhance precision compared to pre-trained models. Conclusions: Chatbots hold promise in AILD support, but our study underscores key areas for improvement. Refinement is needed in providing specific advice, accuracy, and focused up-to-date information. Addressing these shortcomings is essential for enhancing the utility of chatbots in AILD management, guiding future development, and ensuring their effectiveness as clinical decision-support tools.

Introduction and Objectives: With the advent of new therapeutic options for patients with hepatocellular carcinoma (HCC) for intermediate or advanced stages of the Barcelona Clinic Liver Cancer (BCLC), regional real-world data regarding prognostic survival factors are of significant importance. Patients and Methods: A multicenter prospective cohort study was conducted in Latin America including BCLC B or C patients since 15th May 2018. We report here the second interim analysis focusing on prognostic variables and causes of treatment discontinuation. Cox proportional hazard survival analysis was performed, estimating hazard ratios (HR) and 95% confidence intervals (95% CI). Results: Overall, 390 patients were included, 55.1% and 44.9% were BCLC B and C at the time of study enrollment. Cirrhosis was present in 89.5% of the cohort. Among the BCLC-B group, 42.3% were treated with TACE with a median survival since the first session of 41.9 months. Liver decompensation before TACE was independently associated with increased mortality [HR 3.22 (CI 1.64;6.33); P

Introduction and Objectives: Although amoxicillin-clavulanate combination (ACC) is a well-established cause of liver injury, clinicians are unaware of some aspects that explain why its diagnosis may be initially missed, making the patient susceptible to unnecessary exploration or treatment. This study aimed to describe DILI characteristics linked to ACC in the LATINDILI registry. Materials and Methods: We revised data concerning DILI-ACC in the LATINDILI registry during the last decade, looking for information on latency, pattern, severity, and evolution. Baseline characteristics were described using mean, median, and percentages; Student's t-test or a chi-squared test was used to determine the difference between mean and frequencies. A P-value of less than 0.05 was considered statistical significance. Results: We identified 61 DILI-ACC episodes in 60 patients from the LATINDILI registry. The mean age was 58 years (19-90 y), and 54% were male. Median latency was 21 days, with median ALT and ALP at DILI onset of 282 U/L (range 34-2130) and 585 U/L (range 96-1626), respectively; a cholestatic/mixed pattern predominated in 43 cases. In 53 cases, the liver injury appeared with a mean of 13 days (range 2-39 d) after treatment ended. Twenty patients (33%) had allergic immune features, 79% were jaundiced, and 61% required hospitalization. The mean total bilirubin values increased by 7.5 mg/dl (1.5-16) from the onset in 24 of 42 evaluable patients after ten days (range 2-30). Table 1 shows the comparison between groups. Resolution of liver injury occurred on average 64 (14-270) days, one patient did not normalize after 365 days, and no death was consigned. Conclusions: Jaundice linked to a cholestatic/mixed pattern appearing after stopping therapy was a frequent presentation of ACC in our analysis. This clinical presentation may be missed when using ACC and explaining the delayed diagnosis. Worsening bilirubin value is frequent and may be related to longer treatment duration and prolonged latency.

Introduction and Objectives: Idiosyncratic drug-induced liver injury (DILI) caused by antineoplastic and biological agents is an emerging clinical burden in oncologic patients. However, clinical characteristics of DILI due to these drugs remain poorly understood. This study aimed to assess the clinical presentation and outcome of DILI caused by antineoplastic and biological agents in patients enrolled in the prospective Spanish and Latin American DILI registries. Materials and Methods: Information from well-vetted DILI cases caused by antineoplastic and biological agents enrolled in the Spanish DILI Registry (n=38) and the LATINDILI Network (n=33) since their establishment in 2022 was retrieved. Demographics, clinical characteristics, laboratory findings and outcome were analyzed through descriptive statistics. Results: Overall, DILI patients were aged 61±17 years, with Latin American patients slightly younger than Spanish cases (64 vs. 56; p=0.053) and were predominantly men (66%). Novel therapies such as Protein Kinase Inhibitors represented 14% of cases, while Immune Checkpoint Inhibitors caused 6% of DILI cases. Hepatocellular damage predominated (79%), while 12% had a cholestatic injury. Nearly 70% of patients developed jaundice, and 49% were hospitalized. Alanine and aspartate aminotransferase were highly increased (median values 13 and 11 times above the upper limit of normal (ULN), respectively), while alkaline phosphatase showed modest elevations (1.3 times ULN). Total bilirubin was elevated by a median of 3.7-fold ULN. Most of the patients coursed with a moderate injury (46%), and 15% developed severe liver damage. Four Spanish cases, and one from Latin America, had liver-related death (p=0.018). There were no chronic DILI cases, and 71% of patients resolved spontaneously. Conclusions: DILI, due to antineoplastic and biological agents, was more common in men, caused a hepatocellular injury, and usually coursed as a moderate-to-severe liver injury. Latin American cases were slightly younger, while the mortality rate was higher among Spanish DILI patients.

Introduction and Objectives: To achieve WHO's goal of eliminating HCV, innovative strategies must be designed to diagnose and treat more patients. This study aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to Figure 1. Analysis of global DNA methylation. A) Representative dot blot using anti-5mC which recognizes global methylated DNA, anti-IgG as negative control and methylene blue staining as total DNA loading control. B) Graphs shows mean ± standard deviation of 5mC densitometry brand intensity of study groups. C) Graph that represents the percentage of global methylation of the DNA analyzed with ELISA.A one-way ANOVA statistical test and a Tukey post hoc test were performed. Group NT: only received vehicle; Group HCC: damage group induced by weekly administration of DEN and 2-AAF for 12 weeks; and Group HCC/PFD: which received the same treatment as Group HCC, plus PFD (300 mg/kg) (**p

Introduction and Objectives: Previously published regional real-world results of overall survival (OS) in Barcelona Clinic Liver Cancer (BCLC) B and C patients demanded a prospective cohort study nested in a systematic and continuous medical educational networking group. This study aimed to describe and evaluate the treatment decisions in patients with hepatocellular carcinoma (HCC) within BCLC B and C stages. Materials and Methods: A multicenter prospective cohort study, conducted in different Latin American centers from Argentina, Brazil and Colombia, started on 15th May 2018 (delayed recruitment during COVID locked-down period). Patients within BCLC B or C stages were included. Survival, tumor progression and patterns of treatment suspension were evaluated. Results: At this second interim analysis (projected final analysis March 2023), 390 HCC BCLC-B or C patients were included (n=15 excluded); mean age 65 years, 75.6% males and 89.5% cirrhotic. Median OS since HCC diagnosis was 27.2 months. Among BCLC-B patients, the most frequent therapy was transarterial chemoembolization (TACE, 42.3%); 51.8% using drug-eluting beads and 47.4% conventional TACE; with a median OS since 1st TACE of 41.9 months. Similar radiological responses after 1st TACE were observed between both modalities. Overall, 48.2% of the cohort received systemic therapy for HCC (n=188), 23.7% still on BCLC-B stage. The most frequent systemic treatments were Sorafenib (74.5%), atezolizumab bevacizumab (17.5%), and lenvatinib (12.2%), with a median OS since systemic therapy of 15.7 months. Lenvatinib or atezolizumab bevacizumab was used as the second line following sorafenib in 5 and 3 patients, respectively. The most common causes of systemic treatment discontinuation were tumor progression and liver function deterioration (15% to 36.4%). Patterns of tumor progression were not specifically associated with prognosis or treatment discontinuation. Conclusions: Liver function deterioration occurs in a third of patients following systemic therapies. The complexity of treatment decisions underly the need for a multidisciplinary team and the role of hepatologists.

Introduction and Objectives: Chronic hepatitis B and exposure to persistent organic pollutants (COPs) can lead to cellular hepatocarcinoma (HCC), the most common liver tumor. HBV DNA encodes transactivator x, HBx protein. The HBx is required to initiate and maintain HBV replication. Hexachlorobenzene (HCB), COPs´member, is a promoter of hepatic preneoplastic foci. We have shown that HCB increases in rat liver PCNA, TGF-β1, VEGF and neo-angiogenesis in vivo models. This study aimed to analyze in vitro two models of HCC generation -associated with HCB or with the expression of HBx-. Materials and Methods: The HCB effect on cell number (BrdU incorporation by Immunohistochemistry), PCNA (Western blot), TGF-β1 (RT-PCR) was studied in vitro in: 1.1) Huh-7; 1.2) Huh-7 transfected with HBx; 2) HepG2.2.15 (stable expression HBV) and 3) EA-hy926 (endothelial cell). In these last, an inhibitor of TGF-β1-RII (SB431542) was used. In 1.2, 2 and 3 used, 5µM HCB, 24h; in 1, we performed time (30, 60, 90 and 120) and dose (0,005; 0,05; 0,5 and 5µM) curves. Evaluated: a) PCNA protein levels, b) TGF-β1 levels and positive cell number/total cell. Results: In Huh-7, TGF-β1 increased (20%, 69% and 78%, with 0.05, 0.5 and 5µM HCB, respectively) and PCNA (45% and 60%, with 0.5 and 5 µM HCB, respectively). In Huh-7/HBx, PCNA and TGF-β1 increased by 86% and 71%, respectively. In Huh-7/HBx and 5µM HCB, PCNA increased by 120% and TGF-β1 by 91%. In HepG2.2.15 PCNA was overexpressed by 76%. In EA-hy926, PCNA 29% and TGF-β1 by 43% increased. Both effects were prevented by pre-incubating endothelial cells with the specific inhibitor of TGF-B1 RII after HCB 5µM. Conclusions: HCB and HBx induce cell proliferation in vitro. This effect is equivalent for both agents (HCB and HBx) and is enhanced by combining them. The proliferative effect is associated with TGF-β1 increase, which mediates the proliferation generated on both HCC and endothelial cell lines. These findings could partially explain the molecular mechanism involved in human HCC cell proliferation, disease progression and neo-angiogenesis.

Introduction and Objectives: Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins may reduce HCC incidence. Its antitumor activities are controversial and may be mediated by disrupting several hepatocarcinogenic pathways. This study aimed to evaluate in vivo and in vitro the anti-proliferative and anti-angiogenic action of atorvastatin (AT) in the development of HCC as well as its mechanisms of action. Materials and Methods: In vivo model: the pesticide hexachlorobenzene (HCB) was used to promote the development of HCC in Balb/C nude mice inoculated with Hep-G2 cells. Tumor hepatic number, cell proliferation parameters (proliferating cell nuclear antigen, PCNA), cholesterol metabolism (3-hydroxy-3-methylglutaryl-coenzyme-A-reductase, HMGCoAR), angiogenesis and VEGF levels were analyzed. In vitro model: Hep-G2 and Ea-hy926 cells were used to evaluate the effect of AT (2,5; 5 and 5 mg/kg b.w.) on HCB-induced cell proliferation, migration, and vasculogenesis and analyze proliferative parameters. Results: In vivo: AT 5 mg/kg prevented liver growth and tumor development and inhibited PCNA, TGF-β1 and pERK levels increase. AT 5 mg/kg prevented VEGF levels and skin blood vessel formation. In vitro, AT prevented cell proliferation and migration as well as tubular formation in the endothelial cell line by inhibiting the TGF-β1/p ERK pathway. Conclusions: We were able to demonstrate the potential AT anti-proliferative and anti-angiogenic effects in an HCC model and the involvement of TGF-β1 and pERK pathways.

Introduction and Objectives: 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. Materials and Methods: 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. Results: 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). Conclusions: 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.

Background: Hepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive patients, including those with advanced CKD. Sofosbuvir is the backbone of many anti-HCV regimens based on DAAs but it remains unclear whether it is appropriate for HCV-infected patients with stage 4–5 CKD. Study aims and design: We performed a systematic review of the literature with a meta-analysis of clinical studies in order to evaluate the efficacy and safety of SOF-based DAA regimens in patients with stage 4–5 CKD. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcomes were the frequency of SAEs and drop-outs due to AEs (as measures of tolerability). The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses. Results: Thirty clinical studies (n = 1537 unique patients) were retrieved. The pooled SVR12 and SAEs rate was 0.99 (95% confidence intervals, 0.97; 1.0, I2 = 99.8%) and 0.09 (95% CI, 0.05; 0.13, I2 = 84.3%), respectively. The pooled SVR12 rate in studies with high HCV RNA levels at baseline was lower, 0.87 (95% CI, 0.75; 1.0, I2 = 73.3%) (P

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 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.

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.

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

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 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

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

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.

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

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

En el año 2012 la Asociación Argentina para el Estudio de las Enfermedades del Hígado presentó las primeras guías de práctica clínicas referidas al tratamiento de la hepatitis crónica por virus C (HCV). En 2014 se publicó un Consenso Argentino de Hepatitis C, en el que se revisaron todos los temas concernientes a esta enfermedad. Los sucesivos avances en el tratamiento de la hepatitis C crónica nos llevan a actualizar estas guías en forma periódica. Las sociedades científicas dedicadas al estudio de las enfermedades hepáticas: American Association for the Study of Liver Diseases (AASLD), European Association for the Study of the Liver (EASL), Asociación Latinoamericana para el Estudio del Hígado (ALEH), Organización Mundial de la Salud (OMS) y Asian-Pacific Association for the Study of the Liver (APASL), han actualizado sus guías en base a los ultimos tratamientos aprobados por la FDA (Food and Drug Administration) en Estados Unidos y por la EMA (European Medicines Agency) para la hepatitis C. Dado el rápido avance en las investigaciones y desarrollo de nuevos tratamientos, la guía de la AASLD se actualiza periódicamente y sólo se publica online. El manejo de los pacientes con insuficiencia renal crónica avanzada, en hemodiálisis y los pacientes con trasplante renal implica un desafío particular. Si bien los lineamientos para el tratamiento de estos pacientes se encuentran en las recomendaciones presentadas por la AAEEH, esta población requiere algunas consideraciones especiales. Es por ello que el Comité de expertos en hepatitis virales de la AAEEH ha decidido realizar las "Recomendaciones para el Tratamiento de la Hepatitis Crónica por Virus C en pacientes con enfermedad renal crónica, en diálisis (hemodiálisis y diálisis peritoneal) o trasplantados renales" en conjunto con la Sociedad Argentina de Nefrología (SAN), la Asociación Nefrológica de Buenos Aires (ANBA) y la Sociedad Argentina de Trasplantes (SAT). En estas recomendaciones se incluyen los últimos tratamientos recomendados, empleando los antivirales aprobados o en vías finales de aprobación por las autoridades regulatorias en nuestro país. Estas recomendaciones están basadas en el análisis sistemático de la información relevante recientemente publicada. Las referencias se obtuvieron a través de una búsqueda informática en MEDLINE hasta agosto de 2018, de la revisión de las guías de práctica clínica de la AASLD, la EASL, la ALEH, la APASL y la OMS, de la revisión de las presentaciones en congresos internacionales, y de la experiencia publicada de líderes de opinión y expertos en el tratamiento de la hepatitis C. Para caracterizar la evidencia que sustenta cada afirmación, se le asignó a cada recomendación la Clase (reflejando beneficio versus riesgo) y el Nivel de Evidencia (evaluando potencia o certeza), según ha sido recomendado. Se recomendarán los esquemas de tratamiento que se apliquen a la mayoría de los pacientes. Asumimos que el tratamiento de la hepatitis C con estas drogas debe ser indicado y monitoreado por profesionales altamente entrenados en este campo y que cuenten con el soporte tecnológico y multidisciplinario adecuados, en caso contrario, corremos el riesgo de desaprovechar las oportunidades terapéuticas y de no utilizar adecuadamente un recurso caro y limitado.

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 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. Clinicaltrials.gov: NCT04358380.

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.

With the advent of new direct-acting antivirals (DAA) for the treatment of Hepatitis C and their possible use in patients with endstage renal disease and kidney transplantation, the possibility of eradicating this infection in this population opens up. If achieved, it would have an enormous clinical effect given the higher rate of morbidity and mortality that this infection causes in such population, either due to its hepatic or extrahepatic complications, where glomerulopathies play a preponderant role. In this article we have focused on reviewing the pu-blished advances regarding the possible pathogenic role of C virus in the endothelial injury of renal patients, its incidence and clinical effect. We have also reviewed the recent KDIGO Clinical Practice Guideline regarding the treatment criteria and the type of regimen recommended in each scenario.

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.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.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.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.

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 naïve 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 log10 lU/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.

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.

Objetivos. La encefalopatía hepática es una complica - ción neuropsiquiátrica grave en la enfermedad hepática avanzada. Los pacientes afectados presentan alteracio - nes en las funciones psicomotoras e intelectuales. Los ob - jetivos del estudio fueron: a) determinar los valores de referencia del tiempo medio empleado en la ejecución de las pruebas de conexión numérica en nuestra pobla - ción; y b) comparar los resultados de la población de re - ferencia con los obtenidos en cirróticos sin encefalopatía hepática clínica. Materiales y métodos. El estudio se llevó a cabo en dos hospitales de referencia de la Ciudad de La Plata. Se evaluaron las pruebas de conexión nu - mérica A y B (TCN-A y TCN-B) en 112 sujetos sanos y 30 pacientes con cirrosis sin manifestaciones clínicas de encefalopatía hepática. El tiempo para la realiza - ción de las pruebas se midió en segundos. Los resultados fueron comparados por edad, sexo, nivel de educación y las habilidades de motricidad fina en los dos grupos. Resultados. La edad media en el grupo control fue de 45,3 años y 56 (50%) eran mujeres. La edad media de los pacientes con cirrosis fue de 54,5 años; 8 (27%) eran mujeres. En el grupo control, el tiempo medio para completar el TCN-A y el TCN-B fue de 60 s ± 36 s y 140 s ± 60 s, respectivamente. En el grupo con cirrosis, el tiempo medio para completar el TCN-A y el TCN-B fue de 114 s ± 64 s y 232 s ± 87 s, respectivamente (P = 0,00001). El 56,6% de los pacientes cirróticos tomó más de 2 DS para llevar a cabo el TCN-A y el 53,3% más de 2 DS para realizar el TCN-B. Conclusión. Se han obtenido valores de referencia para completar el TCN-A y el TCN-B en la población sana. Los pacien - tes cirróticos sin encefalopatía hepática tardaron el do - ble de tiempo que los controles para completar el TCN- A y el TCN-B. Más de la mitad de nuestros pacientes tendrían encefalopatía hepática mínima.

Background and aims. Genetic variations in the interleukin 28B (IL28B) gene have been associated with viral response to PEG-interferon-a/ribavirin (PR) therapy in hepatitis C virus (HCV) genotype 1 infected patients from North America, Europe and Asia. The importance of these IL28B variants for Argentine patients remains unknown.Material and methods. IL28B host genotypes (rs8099917 and rs12979860) were determined in a population of Argentine patients with European ancestry. Results were analyzed looking for their association with sustained virologic response (SVR) to PR therapy and compared with other baseline hosts’ biochemical, histological and virological predictors of response.Results. We studied 102 patients, 60% were men, and 40% of them were rs8099917 TT and 18% rs12979860 CC. Mean baseline serum HCV RNA was 1.673.092 lU/mL and mean F score was: 2.10 ± 1.18 (21% cirrhotic). SVR rate was higher in rs8099917 TT genotypes (55%) when compared to GT/GG (25%) (p = 0.002) and in rs1512979860 CC (64%) than in CT/TT (30%) (p = 0.004). The univariate analysis showed that rs8099917 TT (OR 3.7; 95 %CI 1.5-8.7; p = 0.002), rs12979860 CC (OR 4.6; 95%CI 1.5-13.7; p = 0.006), low viral load (OR 4.6; 95°% CI 1.7-12.6; p = 0.002) and F0-2 (OR 8.5; 95°% CI 2.3-30.6; p = 0.001) were significantly associated with SVR. In the multivariate analysis, rs12979860 CC, rs8099917 TT, viral load < 400.000 IU/mL and F0-2 were associated with SVR rates (p = 0.029, p = 0.012, p = 0.013 and p = 0.004, respectively).Conclusion. IL28B host genotypes should be added to baseline predictors of response to PR therapy in Latin American patients with European ancestry.

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/aims. No prospective study has been published investigating etiology of HCC in Latin America. The primary aim of this prospective study was to analyze the etiology of liver disease in patients with HCC from our area. Secondary aims were to evaluate staging using Okuda and BCLC classifications; and percentage of patients receiving treatment.Methods. The Governing Board of the Latin American Association for the Study of the Liver designed the protocol. During a 18 month period, all members were invited to load their incident HCC cases on line.Results. 240 cases from 9 countries were uploaded, 174 were male (72.5%), median age was 64 years, interquartile range 57-72. In 85.4% of cases, patients had underlying cirrhosis. Main etiological factors were: HCV in 74 patients (30.8%), alcohol in 49 (20.4%), cryptogenic cirrhosis in 35 (14.6%), HBV in 26 (10.8%), HCV plus alcohol in 14 (5.8%). Considering the combinations, hepatitis C was shown in 91 patients (38%); chronic alcoholism in 68 patients (28%); and hepatitis B in 33 patients (14%). There were no significant differences between the groups in the age at diagnosis. Percentage of male gender was higher in groups of alcohol (94%), HCV plus alcohol (93%) and HBV (85%) than in cryptogenic cirrhosis (60%) and HCV (59%) (p

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

Objetivo: Mostrar la utilidad de la tomografía computada trifásica (TCT) luego del tratamiento con quimioembolización y ablación por radiofrecuencia (RF) del hepatocarcinoma (HCC). Material y métodos: En un período comprendido entre marzo de 2006 y abril de 2008 se controlaron con TCT 90 pacientes que presentaron 148 lesiones nodulares y diagnóstico de hepatocarcinoma; todas fueron tratadas en forma mínimamente invasiva. Para el tratamiento se dividió a los pacientes en dos grupos siguiendo el criterio de Milán. El primer grupo, constituido por 75 pacientes con 109 nódulos, fue tratado con quimioembolización. El segundo grupo, de 15 pacientes y 25 nódulos, fue tratado con ablación por radiofrecuencia. Dentro de nuestra población, hubo un subgrupo de 10 pacientes (14 nódulos) que se trató con ambos métodos. Resultados: De los 90 pacientes tratados, luego de los controles con TC realizados a un mes, 3 meses y cada 3 meses durante dos años, en 63 casos (70%) se observó acumulación homogénea del lipiodol, defecto parcial sin realce o ausencia de realce en la lesión tratada. A estos no se les realizó nuevo procedimiento luego del tratamiento inicial. En los 27 pacientes restantes (30%), se practicó un nuevo tratamiento por visualizarse defecto parcial o ausencia del lipiodol con realce o realce periférico en la fase arterial de la lesión tratada. En este último grupo, 16 pacientes tratados (17,7%) tuvieron nuevo realce nodular en el parénquima hepático restante. Conclusión: La TC en las fases sin contraste y arterial, a un mes y cada 3 meses, permite evaluar la efectividad, enfermedad residual y/o la recaída del hepatocarcinoma luego del tratamiento mínimamente invasivo.Objetive: To show the computed tomography (CT) usefulness after treatment with transcatheter arterial quimioembolization and radiofrequency ablation of hepatocellular carcinoma. Material and methods: In a period between march 2006 to april 2008 a total of 90 patient presenting 148 nodular lesions with diagnosis of hepatocellular carcinoma were controlled with triphasic CT. All the lesions were treated with minimally invasive procedure. For the treatment, the patients were classified in two groups following Milan criteria. The first group, constituted by 75 patients with 109 nodules, was treated with quimioembolization. The second group, of 15 patients with 25 nodules, was treated with radiofrequency ablation. In our population, a subgroup of 10 patients was treated with both methods. Results: Of 90 patients after CT control on a month, 3 months and for each 3 months during 2 years, on 63 cases (70%) was observed homogeneous accumulation of iodized oil, parcial defect without enhancement or absence of enhancement on treated lesions. In these patients a new treatment after initial one was not performed. The remaining 27 patients (30%) underwent new treatment because we founded partial defect or absence of iodized oil with enhancement or peripheral enhancement on arterial phase in treated lesions. In this last group, 16 treated patients (17.7%) had new nodular enhancement on the remaining hepatic parenquimal. Conclusion: The CT unenhanced and the arterial phase on a month and for each 3 months, allow monitoring the effectivenes, residual disease and/or relapse of hepatocellular carcinoma after minimally invasive treatment.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer. The incidence and mortality of HCC are increasing in America countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Clinical care and survival for patients with HCC has advanced considerably during the last two decades, thanks to improvements in patient stratification, an enhanced understanding of the pa-thophysiology of the disease, and because of developments in diagnostic procedures and the introduction of novel therapies and strategies in prevention. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. These LAASL recommendations on treatment of hepatocellular carcinoma are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with liver cancer.

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.

BACKGROUND: The estimated prevalence of HCV infection in Argentina is around 2%. However, higher rates of infection have been described in population studies of small urban and rural communities. The aim of this work was to compare the origin and diversification of HCV-1b in samples from two different epidemiological scenarios: Buenos Aires, a large cosmopolitan city, and O'Brien, a small rural town with a high prevalence of HCV infection. PATIENTS AND METHODS: The E1/E2 and NS5B regions of the viral genome from 83 patients infected with HCV-1b were sequenced. Phylogenetic analysis and Bayesian Coalescent methods were used to study the origin and diversification of HCV-1b in both patient populations. RESULTS: Samples from Buenos Aires showed a polyphyletic behavior with a tMRCA around 1887-1900 and a time of spread of infection approximately 60 years ago. In contrast, samples from ÓBrien showed a monophyletic behavior with a tMRCA around 1950-1960 and a time of spread of infection more recent than in Buenos Aires, around 20-30 years ago. CONCLUSION: Phylogenetic and coalescence analysis revealed a different behavior in the epidemiological histories of Buenos Aires and ÓBrien. HCV infection in Buenos Aires shows a polyphyletic behavior and an exponential growth in two phases, whereas that in O'Brien shows a monophyletic cluster and an exponential growth in one single step with a more recent tMRCA. The polyphyletic origin and the probability of encountering susceptible individuals in a large cosmopolitan city like Buenos Aires are in agreement with a longer period of expansion. In contrast, in less populated areas such as O'Brien, the chances of HCV transmission are strongly restricted. Furthermore, the monophyletic character and the most recent time of emergence suggest that different HCV-1b ancestors (variants) that were in expansion in Buenos Aires had the opportunity to colonize and expand in O'Brien.