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Summary: Healthcare systems in Latin America are broadly heterogeneous, but all of them are burdened by a dramatic rise in liver disease. Some challenges that these countries face include an increase in patients requiring a transplant, insufficient rates of organ donation, delayed referral, and inequitable or suboptimal access to liver transplant programs and post-transplant care. This could be improved by expanding the donor pool through the implementation of education programs for citizens and referring physicians, as well as the inclusion of extended criteria donors, living donors and split liver transplantation. Addressing these shortcomings will require national shifts aimed at improving infrastructure, increasing awareness of organ donation, training medical personnel, and providing equitable access to care for all patients.

Abstract Knowledge of the immunogenicity of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in liver transplant recipients (LTRs) is mainly limited to messenger RNA (mRNA)‐based types. We aimed to evaluate the humoral response in LTRs and to address the use of different doses of mycophenolate (MMF) on the probability of developing anti‐spike immunoglobulin G (IgG). In this prospective cohort study, SARS‐CoV‐2 anti‐spike IgG, neutralizing antibodies (NAs), and nucleocapsid protein (N) were evaluated in LTRs and healthy volunteers 21–90 days after receiving the second vaccine dose of either ChAdOx1 (AstraZeneca), rAd26‐rAd5 (Sputnik V), inactivated BBIBP‐CorV (Sinopharm), or the heterologous combination rAd26/mRNA‐1273 (Sputnik V/Moderna). We collected information regarding clinical data and vaccine side effects. After excluding three LTRs due to a positive N test, 120 LTRs and 27 controls were analyzed. No significant differences were found among groups. Overall, 24 (89%) controls and 74 (62%) LTRs were positive for anti‐spike IgG (p = 0.007). Among LTRs, those immunized with rAd26/mRNA‐1273 presented significantly higher positive serology and NAs when compared with the homologous regimens (91% vs. 55%, p = 0.001; and 1182 IU/ml vs. 446 IU/ml, p = 0.002; respectively). In the multivariate analysis, humoral response was significantly reduced in LTRs who received higher doses of MMF (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.03–0.3; p

Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20–33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732–0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713–0.775; p = 0.042) and Maddrey’s discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691–0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723–0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727–0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724–0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708–0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687–0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805–0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.

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: there is insufficient data regarding bacterial infections in patients with cirrhosis to support recommendations for empiric antibiotic treatments, particularly in Latin America. This study aimed to evaluate bacterial infection's clinical impact and microbiological characteristics, intending to serve as a platform to revise current practices. Materials and Methods: multicenter prospective cohort study of patients with cirrhosis and bacterial infections from Argentina and Uruguay. Patient and infection-related information were collected, focusing on microbiology, antibiotic susceptibility patterns, and outcomes. Results: 472 patients were included. Spontaneous bacterial infections and urinary tract infections (UTIs) were registered in 187 (39.6%) and 116 (24.6%) patients, respectively, representing the most common infections. Of the 256 culture-positive infections, 103 (40.2%) were caused by multidrug-resistant organisms (reaching 50% for UTI), and 181 (70.7%) received adequate initial antibiotic treatment. The coverage of cefepime and ceftriaxone was over 70% for the empirical treatment of community-acquired spontaneous infections, but ceftazidime´s coverage was only 40%. For all UTI cases and for healthcare-associated or nosocomial spontaneous bacterial infections, the lower-spectrum antibiotics that covered at least 70% of the isolations were imipenem and meropenem. During hospitalization, a second bacterial infection was diagnosed in 9.8% of patients, 23.9% required at least one organ support, and 19.5% died. Conclusions: short-term mortality of bacterial infections in patients with cirrhosis is very high, and a high percentage were caused by multidrug-resistant organisms, particularly in UTIs. The information provided might serve to adapt recommendations, particularly related to empirical antibiotic treatment in Argentina and Uruguay. The study was registered in Clinical Trials (NCT03919032).

Introduction and Objectives: Increased utilization of hepatitis C virus (HCV)-positive organ donors has been endorsed as one of several ways to combat organ shortages. However, HCV-positive donors remain poorly characterized. This study aimed to evaluate the prevalence and utilization of HCV antibody (Ab) positive donors in Argentina. Materials and Methods: We performed a cross-sectional study to analyze data from the INCUCAI in Argentina from January 2006 to December 2020. Demographic and allograft characteristics were evaluated, and utilization of HCV Ab-positive donors across Argentina was studied. Anti-HCV (ELISA), was performed on all donors during the procurement process. A stratified analysis according to the type of donor and HCV Ab was done. Results: Overall, 16,140 deceased donors were denounced. Of these, 8627 (53.5%) were organ donors (7802 [90.4%] were effective) and 7513 (46.5%) were tissue donors. Demographic characteristics were age 42 ± 18 years and male/female ratio was 1.59/1. HCV Ab-positive was reported in 0,92% (n=149). The prevalence ratio per period among HCV Ab-positive donors (see graphic 1) showed that the highest prevalence was observed in 2007 (1.3%) and the lowest prevalence was in 2020 (0.1%). Prevalence for HCV Ab-positive among the type of donors was significantly higher in non-effective donors at 5.81% (n=48/825), followed by tissue donors at only 1.01% (n=76/7513) and lower in effective donors at 0.32% (n=25/7802; P

Introduction and Objectives: Although most cases of HCC occur in patients with advanced liver disease and there are effective screening methods, health policies aimed at preventing and detecting HCC are not often on the agenda of government initiatives and policies. This study aimed to explore HCC-related population-wide public health policies, treatment availability, epidemiological surveillance, and awareness campaigns in the Americas. Materials and Methods: We conducted a 43-item survey about HCC among experts from 12 countries. Questions were classified into four categories: policies and civil society (18 questions), clinical guidelines (5 questions), epidemiology (7 questions), and care management (13 questions). The survey was administered using an electronic form in May 2022. Data was collected in a spreadsheet, revised by two independent reviewers, and contrasted with governmental institutions. Results: We obtained 22 responses from 15 out of the 18 countries targeted. A total of 7 (47%) countries had a written national cancer strategy or action plan. Only 4 (27%) countries had a specific written national HCC strategy or action plan, including Argentina, Brazil, Mexico, and the United States. These same four countries also had national clinical guidelines on HCC. HCC is managed by various providers, including Hepatologists (80%), Oncologists (80%), Gastroenterologists (60%), Surgeons (47%), and Palliative medicine (20%). There were important differences in the availability of treatments among countries in the Americas (Figure). Of note, 60% of countries had liver transplantation available for HCC, but only 67% of them had this therapy outside the capital city. Nine (60%) countries had a national disease registry that included HCC. However, only Brazil (7%) had governmental funded awareness campaigns on HCC prevention or screening. Conclusions: Implementation of public health policies on HCC is scarce in the Americas. Important differences in treatments were observed across countries, especially in curative therapies. Our results strongly encourage developing public health policies on HCC in the Americas.

Introduction and Objectives: Argentina is considered an area with a low prevalence of hepatitis B virus (HBV). However, the real prevalence of the disease is unknown. We aimed to study the prevalence of HBV in potential cadaveric donors. Materials and Methods: We performed a cross-sectional study to analyze data from the National Procurement of Transplantation in Argentina from all donors from 2006 to 2020. HBV serologic tests included hepatitis B virus antigen (HBsAg), core antigen-antibody (HBcIgG) and anti-HBs performed during the procurement process. HBV status was defined as 1) active HBV: donors with positive HBsAg; 2) Past HBV infection or false positive: isolated positive HBcIgG; 3) Cured infection anti-HBs+/HBcIgG+. Results: Overall, 16140 deceased donors were denounced. The prevalence of HBsAg was 0.37% (n=60) and of isolated HBcIgG+ was 3.6% (n=575). Among organ donors only, 328 (3.8%) presented isolated HBcIgG-positive serology. Of these, 252 (77%) were effective organ donors. Solid-organ transplants performed using isolated HBcIgG+ donors were 220 kidneys, 124 livers, and 27 intrathoracic organs. There was no significant 5-year graft and patient survival difference between HBcIgG+ receptor (kidney transplant 65% and 81%, and for liver 65% and 83% respectively) and the general population. Anti-HBs data were available in only 4455 donors, of which 19% (N=847) were anti-HBs+. In those patients with positive anti-HBs, HBcIgG was positive in 8.3% (n=369), reflecting past HBV infection. Of the remaining 4086 AntiS available, only 11.7% were positive; that is, they were effectively vaccinated. The Patagonia region presented the highest prevalence of HBsAg, especially in the provinces of La Pampa (2.3%), Santa Cruz (2.2.%), and Tierra del Fuego (2.1.%). Conclusions: The prevalence of HBsAg in deceased donors in Argentina is low. Since the probability of being a donor is random, the prevalence in this population could be close to the real one in the country.

Introduction and Objectives: Alcohol-associated hepatitis (AH) is a severe entity associated with high mortality. Corticosteroids might be used in cases with severe disease and several dynamic models can predict mortality and response to corticosteroids in AH patients. However, there is no consensus on the best of them. This study aimed to evaluate dynamic models to predict response to corticosteroid treatment based on short-term mortality in patients with severe AH based on a worldwide cohort. Materials and Methods: A retrospective cohort study of patients with severe AH (between 2009 – 2019). We included patients who received corticosteroid treatment and calculated the Lille model of day 4 (Lille-4), day 7 (Lille-7) (cut-off value ≥0.45), and the Trajectory of Serum Bilirubin (TSB)(cut-off value ≥0.8 of the ratio between bilirubin at admission and day 7) to predict mortality. We estimated up to 30-day survival using Kaplan-Meier curves, and we performed multivariable analyzes using Cox regression. Specifically, we constructed two models to compare Lille-4 vs. TSB and Lille-7 vs. TSB, adjusting by well-known clinical variables associated with higher mortality in AH (age, sex, and creatinine at admission). Results: 1,066 patients were included (30 centers, 10 countries), age 47.7 ± 10.9 years, 30% women. The MELD score on admission was 25 [21-30]. Responders were considered by Lille-4 49.1%, Lille-7 46.6%, and TSB 55.4%. In the first Cox regression, we observed that Lille-4 and TSB predicted 30-day mortality (HR 3.0, 95%CI: 1.7-5.1; 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: Severe alcohol-associated hepatitis (AH) is an entity with high morbidity and mortality; however, data in Latin America is limited. We aimed to characterize patients hospitalized for AH in a multinational cohort in Latin America. Materials and Methods: Multicenter prospective cohort study. We included patients admitted with severe AH between 2015-2022. Sociodemographic and clinical information was recorded. The analysis included survival analysis using Kaplan-Meier curves. This study was approved by the institutional ethics committee. Results: 470 patients from 24 centers (8 countries: Mexico, Chile, Argentina, Brazil, Peru, Bolivia, Colombia, and Ecuador) were included. Age 49.8 ± 10.6 years, 85.6% of men and 45% had a previous diagnosis of cirrhosis. Median MELD at admission was 26.9 [22-32] points. 26.5% met SIRS criteria and 34.3% had an acute kidney injury (AKI) on admission. Only 36.8% of patients were treated with corticosteroids. Survival at 30 days was 75.0% (95%CI: 70.1-79.3%) and 62.8% (95%CI: 57.1-68.0%) at 90 days. A total of 191 (45.8%) patients presented infections, 31.4% at admission and 24.9% during hospitalization. The most frequent locations of community-acquired infections were respiratory (33.5%), urinary (32.1%), spontaneous bacterial peritonitis (14.9%), and skin (10.5%), while the most frequent pathogens were Escherichia coli (40%), Klebsiella pneumoniae (12%), and Enterococcus (6%). The presence of infection at admission was associated with a decreased survival at 90-days (66.9% versus 48.1%, p=0.0002). AKI at admission was also associated with decreased survival at 90-days (86.8% versus 51.3%, p

Introduction and Objectives: Selecting an empiric antibiotic treatment in patients with cirrhosis and spontaneous bacterial infections is challenging. It is of paramount importance to have local epidemiological data to maximize pathogen coverage while minimizing the unnecessary use of broad-spectrum antibiotics. This study aimed to describe the patterns of antibiotic resistance of spontaneous bacterial infections according to the site of acquisition. Materials and Methods: Analysis of the multicenter prospective cohort study of cirrhotic patients with bacterial infections in Argentina and Uruguay (NCT03919032). Only culture-positive spontaneous infections were included in this study: spontaneous bacterial peritonitis (SBP), spontaneous bacterial empyema (SBE), and spontaneous bacteremia (SB). We estimated the proportion of infections that were sensitive to various antibiotics according to where the infection was acquired: community-acquired (CA), healthcare-associated (HCA), or nosocomial (NOS). Approximately 80% coverage is advisable for empiric treatments in stable patients and 90% for critically-ill patients. Results: The main cohort included 472 patients, of whom 97 presented culture-positive spontaneous infections and were included: with 57 (59%) SBP, 34 (35%) SB, and 4 (6%) SBE. Regarding the site of acquisition, 43% were CA, 36% NOS, and 21% HCA. Gram-positive and negative bacteria were found in 53% and 47% of the infections. The most frequent isolations were Streptococcus spp (26%), E coli (20), K pneumonia (15%), S Aureus (10%), E. faecium (6%) and E. faecalis (4%). Multidrug-resistant organisms (MDROs) were isolated in 35% of the patients. As shown in the table, cefepime and ceftriaxone offer the most rational coverage for CA and HCA infections, and imipenem or meropenem for NOS infections. However, in critically-ill patients, broader-spectrum antibiotics are needed to achieve a coverage closer to 90% (table). Conclusions: We present, for the first time in our region, evidence-based recommendations for the empirical treatment of spontaneous bacterial infections. Prior colonization and/or infections by MDROs might refine even more the antibiotic selection and should be explored.

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: The liver imaging reporting data system (LI-RADS) for hepatocellular carcinoma (HCC) was proposed to standardize and enhance consensus of reporting. However, clinical utility of LI-RADS has not been evaluated in Latin America. We therefore sought to compare LI-RADS categories with histopathology findings in liver transplant (LT) explants in a regional center. Materials and methods: Prospective cohort study conducted between 2012 and 2018 in a single center from Argentina including patients with HCC listed for LT. LI-RADS definitions were applied to magnetic resonance images (MRI) or computed tomography (CT) abdominal scans at time of listing and at final pre-LT reassessment and compared to explant pathology findings; specifically, major nodule (NOD1). Results: Of 130 patients with HCC listed for LT (96.1% with cirrhosis and 35.6% with hepatitis C virus infection), 72 underwent LT. Overall, 65% had imaging HCC diagnosis based on MRI (n = 84), 26% with CT (n = 34) and 9% (n = 12) with both methods. Among LT patients with pre-transplant imaging at our institution (n = 42/72), 69% of the NOD1 were LR-5, 21% LR-4 and 10% LR-3. Definite HCC diagnosis was 50% in LR-3 NOD1 (CI 18–90); none presented microvascular invasion. In LR-4 NOD1, HCC was confirmed in 89% (CI 59–98), of which 11% showed microvascular invasion; whereas in LR-5 NOD1 77% (CI 64–87) had confirmed HCC, 17% with microvascular invasion. Conclusions: LI-RADS was useful to standardize reports; however, no significant differences were observed between LR-4 and LR-5 HCC probability when compared to explant pathology.

Introduction and objectives: After hepatitis A (HAV) mandatory immunization in 2005 in Argentina, the incidence of HAV declined drastically. However, several new autochthonous cases of HAV have been reported since 2017. We aimed to evaluate the clinical and epidemiological characteristics and possible transmission routes of affected patients. Patients or Materials and methods: We performed a cross-sectional study of patients residing in Argentina with acute hepatitis A between 30.06.2017 and 31.12.2018. Results: 66 cases of HAV were registered. Fifty-six patients (86%) were males, with a mean age of 34 ± 12 years old. The most likely routes of transmission were sexual intercourse of men with men, reported by 31 patients. Additionally, 23% and 26% of patients tested positive for HIV and syphilis, respectively. In total, 35% of patients required hospitalization. When assessing outcomes, 79% had a mild presentation and 21% had a severe/fulminant presentation: one patient underwent liver transplantation, and one patient died. Conclusions: Our study describes that during the study period, HAV infection affected predominantly young adults, particularly men who have sex with men. An elevated proportion of them was diagnosed with a concomitant sexually transmitted disease, and several patients had a severe presentation of the disease.

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: Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality in Latin-America, yet the impact of public health policies (PHP) on alcohol consumption and liver disease is unknown. Objectives: To assess the association between alcohol PHP, alcohol consumption, and cirrhosis in Latin-American countries. Methods: We performed an ecological multi-national study including 20 countries in Latin-America (628,466,088 inhabitants). We obtained country-level socio-demographic information from the World Bank Open Data source. Alcohol-related PHP data for countries in Latin-America were obtained from the World Health Organization (WHO) Global Information System of Alcohol and Health (GISAH). We used a fixed-effects model to estimate proportions and multiple linear regression models to examine the association between the number of PHP and outcomes (alcohol intake, and deaths due to cirrhosis & traffic injuries). Results: The prevalence of obesity was 27% and 26.1% among males and females, respectively. The estimated alcohol per capita consumption (APC) among the population 15 years old was 6.8 liters of pure alcohol (5.6 recorded and 1.2 unrecorded). The countries with the highest APC were Uruguay (10.8 liters), Argentina (9.8 liters), and Chile (9.3 liters). The overall prevalence of alcohol use disorders (AUD) was 4.9%. ALD was the main cause of cirrhosis in 64.7% of males and 40.0% of females. A total of 19 (95%) countries have at least one alcohol-related PHP on alcohol. The most frequent PHP were: limiting drinking age (95%), tax control (90%), alcohol and driving (90%), and government monitoring systems (90%)(Table). A higher number of alcohol-related PHP was associated with a lower odds of AUD (OR 0.83, 95%CI:0.73-0.94; p=0.004), lower mortality due to ALD (OR 0.18, 95%CI:0.07-0.46, p

Background: Antibiotic de-escalation is considered a safe strategy that reduces costs and the risk of multi-drug resistant infections. However, its prevalence and associated factors in real-life practice were not reported in patients with cirrhosis in Latin-America. Aims: To estimate the prevalence of antibiotic de-escalation in patients with cirrhosis in real life-practice, and to explore its associated factors. Methods: We performed an analysis of the multicenter prospective cohort study of cirrhotic patients with bacterial infections throughout Argentina and Uruguay (clinicatrials.gov NCT03919032). Patients who died in the first 72 hs from the diagnosis of the infection were excluded. In accordance with guidelines, de-escalation was defined as changing the initially antimicrobials to a narrower spectrum regimen, or suspending one or more of the empirical antibiotics, according to culture results or to other clinical reasons, either in patients with culture-positive or culture-negative bacterial infections. We used inverse probability weighting (IPW) of having a culture-positive infection to estimate its causal effect on de-escalation. Results: We included 450 patients. Most frequent infections were SBP (30.4%), and urinary tract infection (12.9%). Overall, 243 (54%) infections were culture-positive, and 207 (46%) culture-negative. De-escalation was reported in 85 patients (18.9%: 95% CI 15%-22%) at a mean of 3.3 ± 2.4 days from treatment initiation and was more frequent in culture-positive than culture-negative infections (28.4% vs 7.7%, p< 0.001). The table shows the crude analyses of variables associated with de-escalation. Culture-positive infection was strongly and independently associated with de-escalation (ORIPW 6.08; 95% CI: 2.90-12.70; p < 0.001). Conclusions: Antibiotic de-escalation was reported in one-fifth of in-patients with cirrhosis. Given that having a culture-positive infection had a strong effect on de-escalation, efforts should be made to increase the likelihood of obtaining adequate culture samples in a timely manner.

Introduction: Early preventive strict quarantine due to COVID-19 pandemic was implemented in Argentina since March 20th, 2020. Transplant societies and organ procurement organizations were challenged to face this complex scenario and sustain organ donation and transplantation activity. Objectives: We evaluated the impact of complete and preventive lockdown in organ procurement and transplantation before the COVID-19 peak onset. Materials and Methods: We analyzed prospectively collected data from the National Report Agency (INCUCAI). By constructing time series, we compared donation and transplant rates from the years 2010 to 2020, during a same monthly-period between March 3rd and July 20th. We evaluated the effect of preventive lockdown before the peak of COVID-19 curve. Donation rates per million population in these months were also registered for each year. Transplant accessibility was calculated, dividing the total number of transplants and the total number of listed patients. Results: The preventive lockdown was associated with a 34.5% relative reduction (95% CI 26.9-43.2) in organ procurement when compared to 2010-2019 and significantly reduced comparing 2019 [53.3% (CI 44.6-61.6)]. This scenario was even worse in Buenos Aires city and its surroundings, the region most affected by COVID-19. During this period, donation per million population rates decreased from 7.8 in 2019 to 3.3 in 2020. This reduction was even higher in the number of deceased and living donor transplants performed comparing 2019 vs. 2020, with a relative reduction of 62.0% (CI 30.8-89.1) and 68.8% (CI 65.7-71.7), respectively. Conclusions: During this short observation period of 120 days of preventive quarantine, not yet having reached the ''peak'' incidence of COVID-19, a marked reduction in procurement and transplantation rates were observed. Although waiting list mortality was not significantly modified, transplant access has been significantly reduced, showing a future negative trend on waitlist mortality.

Background: Predicting short-term mortality in patients with cirrhosis and bacterial infections is challenging. Aims: To compare the performance of various scores in predicting in-hospital mortality in this population. Methods: We performed an analysis of the multicenter prospective cohort study of patients with cirrhosis with bacterial infections throughout Argentina and Uruguay (clinicatrials.gov.NCT03919032). Patients were classified according to the CLIF criteria as having ACLF or mere acute decompensation (AD). We evaluated the performance of scores of liver disease and infection severity in predicting in-hospital mortality. MELD, MELD-Na, and Quick SOFA (qSOFA) were computed in all patients. CLIF-AD was only computed in patients without ACLF, and CLIF-ACLF only in patients with ACLF. We plotted ROC curves and estimated their area under the curve (AUROC). Results: We included 472 patients: 66% male, mean age 57 ± 12 years. Most frequent infections: SBP (30%) and urinary tract infection (25%). Overall, 332 (70%) patients had acute decompensation, and 140 (30%) ACLF. In-hospital mortality rate was 19%: 41% in patients with ACLF vs 10% in patients with AD (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

Introduction and aim: A pro-oncogenic intestinal microbiome was observed in murine models; however, no specific microbiome in patients with hepatocellular carcinoma (HCC) has been reported. We aimed to compare the gut microbiome found in cirrhotic patients with or without HCC. Materials and methods: From 407 patients with Child Pugh A/B cirrhosis prospectively followed, 25 with HCC (cases) were matched with 25 without HCC (wo-HCC) in a 1:1 ratio according to age, gender, etiology, Child Pugh and severity of portal hypertension. In addition, results were also compared with 25 healthy subjects. Fecal stool samples were sequenced for the V3–V4 region of the microbial 16S rRNA (Illumina MiSeq Platform). Plasma cytokines were quantified including interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). Results: We found a differential abundance in family members of Firmicutes with a 3-fold increase of Erysipelotrichaceae and a 5-fold decrease in family Leuconostocaceae in HCC when compared to wo-HCC controls. Genus Fusobacterium was found to be 5-fold decreased in HCC vs wo-HCC. The ratio bacteriodes/prevotella was increased in HCC. Three operational taxonomic units (OTUs), genus Odoribacter and Butyricimonas were more abundant in HCC, whereas a decreased abundance in Lachnospiraceae family genus Dorea was observed in HCC patients. A Random Forest model trained with differential abundant taxa correctly classified HCC individuals. This pattern was associated with an inflammatory milieu with a putative increased activation of NOD-like receptor pathways. Conclusion: We found a pattern of microbiome linked to inflammation that could be potentially useful as HCC biomarker after follow-up validation studies.

Introduction and aim: Liver transplantation (LT) for acute liver failure (ALF) still has a high early mortality. We aimed to evaluate changes occurring in recent years and identify risk factors for poor outcomes. Material and methods: Data were retrospectively obtained from the Argentinean Transplant Registry from two time periods (1998–2005 and 2006–2016). We used survival analysis to evaluate risk of death. Results: A total of 561 patients were listed for LT (69% female, mean age 39.5 ± 16.4 years). Between early and later periods there was a reduction in wait-list mortality from 27% to 19% (p

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.

Background: The natural history of intrapulmonary vascular dilations (IPVD) and their impact on patient outcomes in the setting of portal hypertension has only been described in small series. Aims: To assess the development of hepatopulmonary syndrome (HPS) in patients with isolated IPVD and to evaluate outcomes of IPVD and HPS among patients evaluated for liver transplantation (LT). Material and methods: Data from a prospective cohort of patients evaluated for LT with standardized screening for HPS were analyzed. IPVDs were defined as the presence of microbubbles in the left atrium > 3 cycles following right atrial opacification. HPS was defined as the presence of IPVD and hypoxemia (Alveolar-arterial gradient ≥ 15 mmHg) in the absence of concomitant cardiopulmonary disease. Results: A total of 104 patients with negative contrast-enhanced echocardiogram (CE) were compared to 63 patients with IPVD and 63 patients with HPS. Only four patients were categorized as ‘severe’ HPS based on degree of hypoxemia (defined as PaO2 < 60 mmHg). Twenty IPVD patients were followed with ABG over a mean duration of 21 months (range 9-43), of whom 7 (35%) subsequently met HPS criteria. Overall unadjusted survival from the time of LT evaluation using multistate survival models that accounted for pre- and post-LT time was not statistically different among the three groups (negative CE, IPVD, and HPS; p > 0.5). Conclusions: Patients with IPVD appear to have a substantial risk of developing oxygenation impairment over time and progress to HPS. In our cohort, survival in patients with HPS and isolated IPVD is not different when compared to those without IPVDs.

Background & rationale. Limited information related to Liver Transplantation (LT) costs in South America exists. Additionally, costs analysis from developed countries may not provide comparable models for those in emerging economies. We sought to evaluate a predictive model of Early Discharge from Hospital after LT (ERDALT = length of hospital stay ≤ 8 days). A predictive model was assessed based on the odds ratios (OR) from a multivariate regression analysis in a cohort of consecutively transplanted adult patients in a single center from Argentina and internally validated with bootstrapping technique.Results. ERDALT was applicable in 34 of 289 patients (11.8%). Variables independently associated with ERDALT were MELD exception points OR 1.9 (P = 0.04), surgery time < 4 h OR 3.8 (P = 0.013), < 5 units of blood products consumption (BPC) OR 3.5 (P = 0.001) and early weaning from mechanical intubation OR 6.3 (P = 0.006). Points in the predictive scoring model were allocated as follows: MELD exception points (absence = 0 points, presence = 1 point), surgery time < 4 h (0-2 points), < 5 units of BPC (0-2 points), and early weaning (0-3 points). Final scores ranged from 0 to 8 points with a c-statistic of 0.83 (95% CI 0.77-0.90; P < 0.0001). Transplant costs were significantly lower in patients with ERDALT (median $23,078 vs. $28,986; P < 0.0001). Neither lower patient and graft survival, nor higher rates of short-term re-hospitalization and acute rejection events after discharge were observed in patients with ERDALT. In conclusion, the ERDALT score identifies patients suitable for early discharge with excellent outcomes after transplantation. This score may provide applicable models particularly for emerging economies.

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.

Background. Incidental hepatocellular carcinoma (iHCC) generates uncertainty over risk of recurrence after liver transplantation (LT). Aim. To compare recurrence between iHCC and confirmed HCC diagnosed prior to transplant based on imaging criteria (cHCC). Material and methods. Fifty-four HCC patients were analyzed from a series of 309 consecutive adult transplanted patients. We developed a recurrence predicting score (RPS) applying ORs based on pathologic risk variables. Results. Incidence of iHCC was 4.8% (n = 15) and overall recurrence 12.9% (cHCC 15.4% and iHCC 7%; P = 0.39). Variables included in the RPS were: microvascular invasion OR 17.8 (1.78-178.97; P = 0.014: 2 points), neural invasion OR 15.5 (1.13-212.17; P = 0.04: 1.5 points), nuclear grade > II OR 9.3 (1.17-74.84; P = 0.035: 1 point), and beyond Up-to 7 criteria OR 13.1 (1.66-103.67; P = 0.015: 1.5 points). Two risk groups were identified: low risk for recurrence (0-1 point) and intermediate-high risk groups (2-6 points). Low risk category remained an independent predictor of recurrence: OR 0.11 (0.01-0.67; P = 0.017); AUROC of 0.75 (0.54-0.96). A tendency towards more patients categorized as low risk group among iHCC patients was observed (69.2%; P = 0.13). Conclusions. In this series iHCC was not associated to lower risk of recurrence when compared to cHCC. We propose application of an RPS as a clinical tool for recurrence risk estimation.

Severe liver dysfunction during pregnancy implies a serious risk for both mother and fetus, and represents a technical and ethical challenge for treating physicians. We report a case of a previously healthy 32-year old woman who was admitted to our hospital with idiopathic fulminant hepatic failure and underwent successful orthotopic liver transplantation (OLT) at gestation week 21. Patient’s and fetus’ immediate postoperative course were relatively uneventful until week six after OLT, when the mother developed oligohydramnios and preeclampsia. At pregnancy week 27, after inducing baby’s lung maturation, a cesarean section was performed with the delivery of an otherwise healthy girl. After 3 years of follow-up, mother and child are leading normal lives with no complications related either to pregnancy or to OLT. We describe the case of a successful emergency liver transplant in a woman during the second trimester of pregnancy, demonstrating that OLT can be a viable option to preserve the life of the mother and an otherwise unviable fetus. Intrauterine baby’s growths until the attainment of a viable gestational age was feasible despite the mother’s fulminant hepatic failure and liver transplant surgery.

Noncirrhotic portal hypertension (NCPH) represents a relatively infrequent group of conditions that causes portal hypertension in the absence of cirrhosis. An association between NCPH and patients infected with human immunodeficiency virus (HIV) has been reported. Six consecutive patients with HIV infection and NCPH were the subject of this series. Case histories, including medication lists, liver biopsy and laboratory data were reviewed. Age at diagnosis was 43 ± 3 years (range, 37-47). Liver disease was diagnosed 12 ± 4 years (range, 8-18) after initiation of antiretroviral therapy (ART). All patients developed esophageal varices, S patients presented at least one bleeding episode and 2 required TIPS. Serum liver tests showed a mean total bilirubin of 1.4 ± .7 mg/dL (range, .S-2.S) and INR was 1.2 ± .14 (range, 1.0-1.4). CD4 count was 326 ± 124 cells/mL (range, 198-467) and all patients presented HIV viral load < 7S copies/mL. Didanosine (ddl) was the most common ART drug being used by 4 patients. Portal vein thrombosis was diagnosed in 2 patients. Hepatic portal sclerosis (HPS) alone was observed in 1 patient, nodular regenerative hyperplasia (NRH) alone in 2 patients and combined HPS/NRH in 3 patients. In conclusion, NCPH should be included in the differential diagnosis of HIV-individuals presenting with clinical manifestations of portal hypertension and well preserved liver synthetic function. Prolonged exposure to ART, specially ddI, can play a pathogenic role. Rarely, liver synthetic function is sufficiently severe to warrant liver transplantation.