Search

The most common primary liver tumors are hepatocellular carcinoma and cholangiocarcinoma. They constitute the sixth most common neoplasia and the third cause of cancer-related deaths worldwide. Although both tumors may share etiologic factors, diagnosis, prognostic factors, and treatments, they differ substantially in determining distinctive clinical management. In recent years, significant advances have been made in the management of these neoplasms, particularly in advanced stages. In this review, we focus on the most relevant diagnostic, prognostic, and treatment aspects of both, hepatocellular carcinoma and cholangiocarcinoma, underlying their applicability in Latin America.

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: Recently, two composite models, the alpha-fetoprotein (AFP) score and the Metroticket 2.0, have been proposed to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). This study aimed to compare both models in their predictive performance of post-LT outcomes and their net reclassification of risk of recurrence. Materials and Methods: This multicenter cohort study included 2444 adult patients who underwent LT for HCC in Europe and Latin America. The discrimination power of each model was estimated using adapted Harrell c-statistics and the NRI for recurrence was compared considering each model´s threshold assessed at listing and at last pre-LT reassessment. Results: At listing, although the Metroticket 2.0 showed a higher discrimination power for HCC recurrence compared to the AFP score, no differences were observed comparing each model's thresholds. At the last tumor evaluation, c-statistics did not significantly differ. Overall, predictive gaps and overlaps were observed between the model's thresholds. At listing and at last pre-LT reassessment, the Metroticket 2.0 did not show a significant gain on the NRI. Patients meeting both composite model´s thresholds either within or beyond the Milan criteria showed the lowest risk of HCC recurrence [SHR of 0.28 (95% CI 0.22-0.36; P

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: Liver transplantation (LT) selection models for hepatocellular carcinoma (HCC) have not been proposed to predict waitlist dropout due to tumor progression. This study aimed to compare the alfa-fetoprotein (AFP) model and other pre-LT models in their prediction of HCC dropout. Materials and Methods: A multicenter cohort study was conducted in 20 Latin American transplant centers, including 994 listed patients for LT with HCC from 2012 to 2018. Longitudinal tumor characteristics and patterns of progression were recorded at the time of listing, after treatments and at last follow-up over the waitlist period. Competing risk regression models were performed, and the model's discrimination was compared by estimating Harrell's adapted c-statistics. Results: HCC dropout rate was significantly higher in patients beyond [24% (95% CI 16-28)] compared to those within Milan criteria [8% (95% IC 5-12%); P2 [adjusted SHR of 3.17 (CI 2.13-4.71)], c-index of 0.71 (95% CI 0.65-0.77; P=0.09 vs. Milan). Similar discrimination power for HCC dropout was observed between the AFP score and the Metroticket 2.0 model. In patients within Milan, an AFP score >2 points discriminated two populations with a higher risk of HCC dropout [SHR 1.68 (95% CI 1.08-2.61)]. Conclusions: Pre-transplant selection models similarly predicted HCC dropout. However, the AFP model can discriminate a higher risk of dropout among patients within Milan criteria.

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: 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.

Background & Aims: Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model’s original thresholds. Methods: This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell’s adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model’s original thresholds. Results: During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria (p

Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3–6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101–1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber’s c-index was 0.76 (95% CI 0.72–0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72–0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1–2 points; 15.1%), high (3–6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber’s c-index of 0.78; 95% CI 0.73–0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria. Clinical Trials Registration: NCT03775863. Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT.

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.

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.

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

Background & Aims: Good outcomes after liver transplantation (LT) have been reported after successfully downstaging to Milan criteria in more advanced hepatocellular carcinoma (HCC). We aimed to compare post-LT outcomes in patients receiving locoregional therapies (LRT) before LT according to Milan criteria and University of California San Francisco downstaging (UCSF-DS) protocol and ‘all-comers’. Methods: This multicentre cohort study included patients who received any LRT before LT from Europe and Latin America (2000–2018). We excluded patients with alpha-foetoprotein (AFP) above 1,000 ng/ml. Competing risk regression analysis for HCC recurrence was conducted, estimating subdistribution hazard ratios (SHRs) and corresponding 95% CIs. Results: From 2,441 LT patients, 70.1% received LRT before LT (n = 1,711). Of these, 80.6% were within Milan, 12.0% within UCSF-DS, and 7.4% all-comers. Successful downstaging was achieved in 45.2% (CI 34.8–55.8) and 38.2% (CI 25.4–52.3) of the UCSF-DS group and all-comers, respectively. The risk of recurrence was higher for all-comers (SHR 6.01 [p

Introduction and Objectives: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the impact of SARS-CoV-2 infection on clinical outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. Patients: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. Results: Overall, 4.6%(CI 3.7-5.6) subjects had cirrhosis (n=96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14-25). Mortality was 47% in patients with cirrhosis compared to 16% in those without cirrhosis (P30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P

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 & Aims: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. Methods: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. Results: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). Conclusions: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. Lay summary: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.

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 & 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.

Hepatocellular carcinoma (HCC) is one of the main cancer-related causes of death worldwide. Thus, there is a constant search for improvement in screening, diagnosis, and treatment strategies to improve the prognosis of this malignancy. The identification of useful biomarkers for surveillance and early HCC diagnosis is still deficient, with available serum biomarkers showing low sensitivity and heterogeneous specificity despite different cut-off points, even when assessed longitudinally, or with a combination of serum biomarkers. In contrast, HCC biomarkers used for prognostic (when associated with clinical outcomes) or predictive purposes (when associated with treatment response) may have an increased clinical role in the near future. Furthermore, some serum biomarkers are already implicated as a treatment selection tool, whether to provide access to certain therapies or to assess clinical benefit after treatment. In the present review we will discuss the clinical utility and foreseen future of HCC biomarkers implicated in surveillance, diagnosis, prognosis, and post-treatment assessment.

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.

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.

Introduction. La evaluación de la función renal al año post-trasplante hepático (TH) predice el desarrollo de injuria renal crónica y progresiva a largo plazo. Objetivo. Evaluar variables predictoras pre- y post-TH de desarrollo de disfun - ción renal (DR) en pacientes cirróticos luego del TH. Mé - todos. Entre junio de 2005 y junio de 2010, 104 pacientes cirróticos fueron incluidos de un total 268 pacientes adultos trasplantados de hígado. La DR se definió cuando la tasa de filtrado glomerular (TFG) era de