Disparities in screening and risk stratification for hispanic adults with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AIMS: Cut-points for non-invasive tests (NITs) for risk stratification in metabolic dysfunction-associated steatotic liver disease (MASLD) were derived from predominantly non-Hispanic populations. It is unknown if these cut-points perform adequately in Hispanic individuals. We assessed the performance characteristics of current NIT cut-points among Hispanic patients and determined whether they could be further optimized. APPROACH RESULTS: We prospectively enrolled 244 adults with biopsy-proven MASLD. Participants underwent a research visit with magnetic resonance elastography (MRE) and vibration controlled transient elastography (VCTE). Histology and imaging assessments were conducted centrally. Diagnostic performance was evaluated by area under the receiver-operating curve (AUROC) and optimal cut-points were identified by Youden J analysis. The mean (±SD) age and body mass index were 52.6 (±13) and 31.6 (±4.6) kg/m2. Overall, 40% had diabetes, 31% (N=75) were Hispanic. 40% of Hispanic and 28.4% of non-Hispanic patients had significant fibrosis. To detect significant fibrosis, MRE and VCTE exhibited significantly lower accuracy in Hispanic versus non-Hispanic participants (AUROC: MRE, 0.87 vs. 0.98, p=0.01; VCTE, 0.78 vs. 0.92, p=0.02). Clinical care algorithms yielded high false-negative rates among Hispanic participants (14% with low-risk FIB-4 and 21% with low-risk VCTE had advanced fibrosis on biopsy). Cut-points of 2.73 kPa for MRE and 6.9 kPa for VCTE were optimal to detect significant fibrosis in Hispanic individuals. Findings were validated in a Latin American cohort. CONCLUSIONS: Lower NIT cut-points may be needed to optimize surveillance for significant fibrosis due to MASLD in Hispanic populations commensurate with their higher burden and severity of disease.

Sex and ethnic disparities in hepatitis B evaluation and treatment across the world.

BACKGROUND & AIMS: Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of evaluation and treatment in patients from the REAL-B consortium. METHODS: This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses. RESULTS: We analyzed 12,566 adult treatment-naïve patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio [aOR] 1.13, p = 0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p <0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p <0.001). CONCLUSIONS: Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed. IMPACT AND IMPLICATIONS: Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.

Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study.

BACKGROUND & AIMS: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. METHODS: We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. RESULTS: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P = .40) and HCC incidence rates (5.1% vs 4.4%; P = .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17-1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03-1.31; P = .016), but VR and HCC risks were similar. CONCLUSIONS: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.

Integrated analysis of the transcriptome and its interaction with the metabolome in metabolic associated fatty liver disease: Gut microbiome signatures, correlation networks, and effect of PNPLA3 genotype.

Interactions between communities of the gut microbiome and with the host could affect the onset and progression of metabolic associated fatty liver disease (MAFLD), and can be useful as new diagnostic and prognostic biomarkers. In this study, we performed a multi-omics approach to unravel gut microbiome signatures from 32 biopsy-proven patients (10 simple steatosis -SS- and 22 steatohepatitis -SH-) and 19 healthy volunteers (HV). Human and microbial transcripts were differentially identified between groups (MAFLD vs. HV/SH vs. SS), and analyzed for weighted correlation networks together with previously detected metabolites from the same set of samples. We observed that expression of Desulfobacteraceae bacterium, methanogenic archaea, Mushu phage, opportunistic pathogenic fungi Fusarium proliferatum and Candida sorbophila, protozoa Blastocystis spp. and Fonticula alba were upregulated in MAFLD and SH. Desulfobacteraceae bacterium and Mushu phage were hub species in the onset of MAFLD, whereas the activity of Fonticula alba, Faecalibacterium prausnitzii, and Mushu phage act as key regulators of the progression to SH. A combination of clinical, metabolomic, and transcriptomic parameters showed the highest predictive capacity for MAFLD and SH (AUC = 0.96). In conclusion, faecal microbiome markers from several community members contribute to the switch in signatures characteristic of MAFLD and its progression towards SH.

[Epidemiology of patients with hepatocellular carcinoma in a University hospital]. / Epidemiología de pacientes con hepatocarcinoma en un Hospital Universitario.

Hepatocellular carcinoma is the most common primary liver tumor, with 905 677 diagnosed cases and 830 180 deaths, in 2020 worldwide. In Argentina, it accounts for the 9th cause of death for cancer in men and the 10th in women. Unlike other highly-prevalent tumors, scientific evidence for most therapeutic options is limited mainly to small cohorts and retrospective studies. The aim of this study is to characterize and describe epidemiologically patients with diagnosis of hepatocellular carcinoma in the Italian Hospital of Buenos Aires during a 12-year period. Overall survival for our cohort was 58%, 46%, and 36% at 1, 3 and 5 years respectively. Average survival for patients receiving palliative treatment was 5 months, while for those who received either non-curative or curative treatment was 23 and 75 months respectively. Recurrence-free survival for those patients who underwent a curative treatment was 89%, 76% y 61% at 1, 3 and 5 years. A thorough analysis of etiology, risk factors, incidence, mortality and treatment was made. The study's importance lies in its large sample size, quantity and quality of data, and will most certainly stimulate the development of local studies in hepatocellular carcinoma.

El carcinoma hepatocelular (HCC) es el tumor primario más frecuente del hígado, con 905 677 casos diagnosticados en 2020, en todo el mundo, y 830 180 muertes. Es responsable de la novena causa de muerte por cáncer en los hombres y la décima en mujeres en Argentina. A diferencia de otros tumores de alta prevalencia, la evidencia científica acerca del HCC se limita principalmente a pequeñas cohortes y estudios retrospectivos. El objetivo de este estudio fue describir epidemiológicamente a aquellos pacientes con diagnóstico de HCC en el Hospital Italiano de Buenos Aires en un periodo de 12 años. La supervivencia global para nuestra cohorte fue de 58, 46 y 36% a 1, 3 y 5 años respectivamente. El promedio de supervivencia en pacientes con tratamiento paliativo fue de 5 meses, 23 para aquellos que recibieron tratamientos no curativos y 75 meses para los que recibieron tratamientos curativos. El porcentaje de pacientes libres de enfermedad a 1, 3 y 5 años fue de 89%, 76% y 61% respectivamente. Se realizó un estudio minucioso de la etiología, factores de riesgo, incidencia, mortalidad y tratamientos realizados. Su importancia yace en su tamaño muestral, calidad y cantidad de información disponible.

Epidemiología de pacientes con hepatocarcinoma en un hospital Universitario / Epidemiology of patients with hepatocellular carcinoma in a University hospital

Resumen El carcinoma hepatocelular (HCC) es el tumor primario más frecuente del hígado, con 905 677 casos diagnosticados en 2020, en todo el mundo, y 830 180 muertes. Es responsable de la novena causa de muerte por cáncer en los hombres y la décima en mujeres en Argentina. A diferencia de otros tumo res de alta prevalencia, la evidencia científica acerca del HCC se limita principalmente a pequeñas cohortes y estudios retrospectivos. El objetivo de este estudio fue describir epidemiológicamente a aquellos pacientes con diagnóstico de HCC en el Hospital Italiano de Buenos Aires en un periodo de 12 años. La supervivencia global para nuestra cohorte fue de 58, 46 y 36% a 1, 3 y 5 años respectivamente. El promedio de supervivencia en pacientes con tratamiento paliativo fue de 5 meses, 23 para aquellos que recibieron tratamientos no curativos y 75 meses para los que recibieron tratamientos curativos. El porcentaje de pacientes libres de enfermedad a 1, 3 y 5 años fue de 89%, 76% y 61% respectivamente. Se realizó un estudio minucioso de la etiología, factores de riesgo, incidencia, mortalidad y tratamientos realizados. Su importancia yace en su tamaño muestral, calidad y cantidad de información disponible.

Abstract Hepatocellular carcinoma is the most common primary liver tumor, with 905 677 diagnosed cases and 830 180 deaths, in 2020 worldwide. In Argentina, it accounts for the 9th cause of death for cancer in men and the 10th in women. Unlike other highly-prevalent tumors, scientific evidence for most therapeutic options is limited mainly to small cohorts and retrospective studies. The aim of this study is to characterize and describe epidemiologically patients with diagnosis of hepatocellular carcinoma in the Italian Hospital of Buenos Aires during a 12-year period. Overall survival for our cohort was 58%, 46%, and 36% at 1, 3 and 5 years respectively. Average survival for patients receiving palliative treatment was 5 months, while for those who received either non-curative or curative treatment was 23 and 75 months respectively. Recurrence-free survival for those patients who under went a curative treatment was 89%, 76% y 61% at 1, 3 and 5 years. A thorough analysis of etiology, risk factors, incidence, mortality and treatment was made. The study's importance lies in its large sample size, quantity and quality of data, and will most certainly stimulate the development of local studies in hepatocellular carcinoma.

Effectiveness of entecavir vs tenofovir disoproxil fumarate for functional cure of chronic hepatitis B in an international cohort.

INTRODUCTION: Both entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line therapies for chronic hepatitis B (CHB), but their comparative effectiveness with regards to hepatitis B surface antigen (HBsAg) seroclearance remains unclear. METHODS: This international multicenter cohort study enrolled 7697 treatment-naïve CHB patients (median age 50 years; male 66.75%) initiated on either ETV (n = 5430) or TDF (n = 2267) without baseline malignancy or immunosuppression from 23 centers across 10 countries or regions. Patients were observed for HBsAg seroclearance until death, loss to follow-up, or treatment discontinuation or switching. The incidences of HBsAg seroclearance were adjusted for competing mortality and compared between ETV and TDF cohorts with inverse probability of treatment weighting (IPTW) and also by multivariable regression analysis. RESULTS: The study population was followed up for a median duration of 56.1 months with 36,929 11 person-years of observation. HBsAg seroclearance occurred in 70 ETV-treated and 21 TDF-treated patients, yielding 8-year cumulative incidence of 1.69% (95% confidence interval [CI] 1.32-2.17) for ETV and 1.34% (95% CI 0.85-2.10%), for TDF (p = 0.58). In the IPTW analysis with the two study cohorts more balanced in background covariates, the age-adjusted hazard ratio (HR) of TDF versus ETV for HBsAg seroclearance was 0.91 (95% CI 0.50-1.64; p = 0.75). Furthermore, there was no significant difference between the two medications in the multivariable competing risk regression model (adjusted sub-distributional HR 0.92 for TDF vs. ETV; 95% CI 0.56-1.53; p = 0.76). CONCLUSIONS: ETV and TDF did not differ significantly in the incidence of HBsAg seroclearance, which rarely occurred with either regimen.

Chronic kidney disease (CKD) and chronic kidney insufficiency (CKI) diagnosing equation in cirrhotic patients.

Cirrhotic patients can develop acute kidney injury (AKI), and chronic kidney disease (CKD). Therefore, renal functional evaluation is crucial in cirrhotic patients. However, serum creatinine and urea levels, as well as measured or estimated glomerular filtration rate is not reliable renal functional markers in these patients compared to other patient groups. In the present study, four original equations are designed and tested for screening chronic kidney disease (CKD) and chronic kidney insufficiency (CKI) in stable cirrhotic patients. MATERIAL & METHOD: estimated GFR (CKD-EPI creatinine and cystatin equations) were recorded in 175 adult stable patients suffering from cirrhosis, and these patients were classified as presenting or not CKD and CKI after evaluation by two independent nephrologists. Based on these data, the variables with the significant discriminating capability to identify CKD and CKI (based on creatinine and cystatin) were detected by applying the Student's t-test for two independent groups, later confirmed by the lambda test of Wilks, in order to obtain the renal function equations. RESULTS: CKD equation (creatinine) = 7.094238-0.043104 × CKD-EPI creatinine - 0.057537 × haematocrit. CKD equation (cystatin) = 8.375074-0.117218 × CKD-EPI cystatin. CKI equation (creatinine) = 0.428389-0.043214 × CKD-EPI creatinine +0.183051 × Child-Pugh score + 0.050162 × age (in years). CKI equation (cystatin) = 9.169579-0.139319 × CKD-EPI cystatin. CONCLUSION: Simple and reliable equations have been obtained for screening chronic kidney disease and chronic kidney insufficiency in cirrhotic patients.

Resistencia antimicrobiana y producción porcina de cría intensiva / Antimicrobial resistance and intensive swine production: mini review

Introducción: el impacto de la resistencia antimicrobiana (RAM) generará un aumento de las muertes relacionadas de 10 millones anuales hacia 2050. El 70% de la dispensación de antimicrobianos (ATB) se utiliza en la agroveterinaria y no en salud humana. Es fundamental conocer la portación de RAM en trabajadores de cría de animales y en los animales, para acciones tempranas de salud pública. Métodos: bajo metodología PRISMA se realizó la búsqueda bibliográfica en distintas fuentes disponibles hasta octubre de 2020. Se priorizaron revisiones sistemáticas, metanálisis, ensayos clínicos y estudios observacionales para determinar la RAM en trabajadores de cría de cerdos. De 990 artículos identificados se incluyeron 8 estudios. Resultados: la tasa de colonización por Staphylococcus aureus resistente a la meticilina (SAMR) en trabajadores fue mayor que la de la población general. La prevalencia de SAMR fue significativamente mayor en trabajadores en contacto directo con animales y los de granjas de cría intensiva con respecto a los de extensiva. En cerdos, la prevalencia de RAM en cría intensiva fue significativamente mayor que la de los de cría extensiva. También fue significativa la asociación entre el suministro de antibióticos en la cría intensiva y la presencia de RAM. Las granjas de más de 1250 cerdos presentaron mayor prevalencia de RAM (p < 0,001). El fenotipo de SAMR en cerdos, trabajadores y el ambiente fue el mismo. Conclusiones: existe evidencia de asociación entre la producción agrícola de cría intensiva y la RAM en cerdos y trabajadores. No se encontraron estudios de vigilancia epidemiológica en la Argentina en trabajadores de cría de animales. (AU)

Introduction: it is estimated that the impact of antimicrobial resistance (AMR) will generate an increase of 10 million deaths by 2050, being reflected to a greater extent in low-income countries. 70% of the annual use of antimicrobials is concentrated in agroveterinary but not in human health. Considering the presence of AMR in ranchers and agricultural workers is essential for early public health actions. Methods: using the PRISMA methodology, bibliography was searched in different sources until October 2020. Systematic reviews, meta-analyses, clinical trials and observational studies were prioritized to determine AMR in pig workers. Eight studies of the 990 found have been included. Results: the rate of colonization by methicillin-resistant Staphylococcus aureus (MRSA) in farming workers was higher than the general population. MRSA prevalence was significantly higher in workers who reported direct contact with animals. And also in those workers of intensive farms compared to those of extensive farms. The same situation is observed in swines, in which the prevalence of AMR in intensive farming was significantly higher than in extensive farming. The association between the supply of antibiotics in intensive farming workers and the presence of AMR was also significant. Farms with more than 1,250 swines had a higher prevalence of AMR (p<0.001). The MRSA phenotype found in swine, agricultural workers, and the environment was the same. Conclusions: there is scientific evidence of an association between agricultural production in intensive livestock farming and AMR in swine and farming workers. There aren't Argentine studies of epidemiological surveillance in farming workers. (AU)

Sarcopenia HIBA score predicts sarcopenia and mortality in patients on the liver transplant waiting list.

Sarcopenia is a prevalent condition that predicts prognosis in patients awaiting liver transplantation (LT). The gold standard for the diagnosis of sarcopenia is the assessment of the muscular area at L3 with computed tomography (CT) scan (skeletal muscle index [SMI]), but the routine use of CT scan is limited in clinical practice. Thus, we designed a single-center observational study aimed to evaluate the clinical factors associated with the presence of sarcopenia by SMI, and to build a score capable of predicting or excluding the presence of sarcopenia in patients on the LT waiting list (WL). Binary logistic regression analysis was performed to establish the factors independently associated with sarcopenia, and the Sarcopenia Hospital Italiano de Buenos Aires (HIBA) score was built from the resulting model after internal validation analysis by bootstrapping and correction for optimism. The predictive capability of mortality on the WL was evaluated with competing risk regression analysis. A total of 215 patients with cirrhosis on the LT WL were included. The independent factors associated with the presence of sarcopenia were male sex (odds ratio [OR]: 6.09, p < 0.001), body mass index (OR: 0.74, p < 0.001), Child Pugh (OR: 1.44, p < 0.001), and the ratio creatinine/Cystatin C (OR: 0.03, p = 0.007). The Sarcopenia HIBA score constructed with these variables showed an area under the curve of 0.862. During follow-up, 77 (36%) patients underwent LT, 46 (21%) died, and 92 (43%) remained alive. After adjusting for Model for End-Stage Liver Disease-Sodium, Sarcopenia HIBA score was an independent predictor of WL mortality (subhazard ratio: 1.19; 95% confidence interval 1.01-1.40; p = 0.042). Sarcopenia HIBA score is an easy-to-use, objective, and reliable diagnostic and predictive tool that can be useful to improve the prognostic evaluation and allow identifying a group of patients with a higher risk of death while awaiting LT.

Do changes in inflammatory markers predict hepatocellular carcinoma recurrence and survival after liver transplantation?

BACKGROUNDS/AIMS: The role of inflammation in malignant cell proliferation has been well described. High values of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) as markers of systemic inflammation have shown associations with unfavorable long-term outcomes. The purpose of this study was to determine values of NLR and PLR evaluated prior to and after surgery and their associations with mortality and recurrence rates of liver transplant patients with hepatocellular carcinoma (HCC). METHODS: A total of 105 patients with HCC who underwent orthotopic liver transplantation (OLT) were retrospectively reviewed. NLR and PLR values were obtained from complete blood counts prior to and after surgery. Overall survival (OS) and recurrence-free survival (RFS) in relation with delta NLR and PLR were estimated. RESULTS: Serum alpha-fetoprotein levels > 100 ng/mL (p = 0.014) and lymphovascular emboli in the specimen (p = 0.048) were identified to be significant predictors of RFS. Child-Pugh score (p = 0.016) was found to be an independent factor associated with poorer OS. An increasing delta PLR was associated with worse RFS, although it showed no significant association with OS. CONCLUSIONS: The analysis of PLR as a continuous variable may predict recurrence outcomes in patients undergoing OLT for HCC. It is more representative than isolated values.

International study on the outcome of locoregional therapy for liver transplant in hepatocellular carcinoma beyond Milan criteria.

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 <0.0001]) and not significantly higher for the UCSF-DS group (SHR 1.60 [p = 0.32]), compared with patients remaining within Milan. The all-comers presented more frequent features of aggressive HCC and higher tumour burden at explant. Among the UCSF-DS group, an AFP value of ≤20 ng/ml at listing was associated with lower recurrence (SHR 2.01 [p = 0.006]) and better survival. However, recurrence was still significantly high irrespective of AFP ≤20 ng/ml in all-comers. CONCLUSIONS: Patients within the UCSF-DS protocol at listing have similar post-transplant outcomes compared with those within Milan when successfully downstaged. Meanwhile, all-comers have a higher recurrence and inferior survival irrespective of response to LRT. Additionally, in the UCSF-DS group, an ALP of ≤20 ng/ml might be a novel tool to optimise selection of candidates for LT. CLINICAL TRIAL NUMBER: This study was registered as part of an open public registry (NCT03775863). LAY SUMMARY: Patients with more extended HCC (within the UCSF-DS protocol) successfully downstaged to the conventional Milan criteria do not have a higher recurrence rate after LT compared with the group remaining in the Milan criteria from listing to transplantation. Moreover, in the UCSF-DS patient group, an ALP value equal to or below 20 ng/ml at listing might be a novel tool to further optimise selection of candidates for LT.

Failure in all steps of hepatocellular carcinoma surveillance process is frequent in daily practice.

INTRODUCTION AND OBJECTIVES: Failures at any step in the hepatocellular carcinoma (HCC) surveillance process can result in HCC diagnostic delays and associated worse prognosis. We aimed to estimate the prevalence of surveillance failure and its associated risk factors in patients with HCC in Argentina, considering three steps: 1) recognition of at-risk patients, 2) implementation of HCC surveillance, 3) success of HCC surveillance. METHODS: We performed a multi-center cross-sectional study of patients at-risk for HCC in Argentina seen between10.01.2018 and 10.30.2019. Multivariable logistic regression analysis was used to identify correlates of surveillance failure. RESULTS: Of 301 included patients, the majority were male (74.8%) with a mean age of 64 years old. At the time of HCC diagnosis, 75 (25%) patients were unaware of their diagnosis of chronic liver disease, and only 130 (43%) patients were under HCC surveillance. Receipt of HCC surveillance was significantly associated with follow-up by a hepatologist. Of 119 patients with complete surveillance, surveillance failure occurred in 30 (25%) patients. Surveillance failure was significantly associated with alpha fetoprotein ≥20 ng/mL (OR 4.0, CI 95% 1.43-11.55). CONCLUSIONS: HCC surveillance failure was frequent in all the evaluated steps. These data should help guide strategies to improve the implementation and results of HCC surveillance in our country.

Liver transplantation for hepatocellular carcinoma: impact of expansion criteria in a multicenter cohort study from a high waitlist mortality region.

This study aimed to compare liver transplantation (LT) outcomes and evaluate the potential rise in numbers of LT candidates with hepatocellular carcinoma (HCC) of different allocation policies in a high waitlist mortality region. Three policies were applied in two Latin American cohorts (1085 HCC transplanted patients and 917 listed patients for HCC): (i) Milan criteria with expansion according to UCSF downstaging (UCSF-DS), (ii) the AFP score, and (iii) restrictive policy or Double Eligibility Criteria (DEC; within Milan + AFP score ≤2). Increase in HCC patient numbers was evaluated in an Argentinian prospective validation set (INCUCAI; NCT03775863). Expansion criteria in policy A showed that UCSF-DS [28.4% (CI 12.8-56.2)] or "all-comers" [32.9% (CI 11.9-71.3)] had higher 5-year recurrence rates compared to Milan, with 10.9% increase in HCC patients for LT. The policy B showed lower recurrence rates for AFP scores ≤2 points, even expanding beyond Milan criteria, with a 3.3% increase. Patients within DEC had lower 5-year recurrence rates compared with those beyond DEC [13.3% (CI 10.1-17.3) vs 24.2% (CI 17.4-33.1; P = 0.0006], without significant HCC expansion. In conclusion, although the application of a stricter policy may optimize the selection process, this restrictive policy may lead to ethical concerns in organ allocation (NCT03775863).

Recurrence of hepatocellular carcinoma after liver transplantation: Prognostic and predictive factors of survival in a Latin American cohort.

BACKGROUND & AIM: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has a poor prognosis, and the adjusted effect of different treatments on post-recurrence survival (PRS) has not been well defined. This study aims to evaluate prognostic and predictive variables associated with PRS. METHODS: This Latin American multicenter retrospective cohort study included HCC patients who underwent LT between the years 2005-2018. We evaluated the effect of baseline characteristics at time of HCC recurrence diagnosis and PRS (Cox regression analysis). Early recurrences were those occurring within 12 months of LT. To evaluate the adjusted treatment effect for HCC recurrence, a propensity score matching analysis was performed to assess the probability of having received any specific treatment for recurrence. RESULTS: From a total of 1085 transplanted HCC patients, the cumulative incidence of recurrence was 16.6% (CI 13.5-20.3), with median time to recurrence of 13.0 months (IQR 6.0-26.0). Factors independently associated with PRS were early recurrence (47.6%), treatment with sorafenib and surgery/trans-arterial chemoembolization (TACE). Patients who underwent any treatment presented "early recurrences" less frequently, and more extrahepatic metastasis. This unbalanced distribution was included in the propensity score matching, with correct calibration and discrimination (receiving operator curve of 0.81 [CI 0.72;0.88]). After matching, the adjusted effect on PRS for any treatment was HR of 0.2 (0.10;0.33); P < .0001, for sorafenib therapy HR of 0.4 (0.27;0.77); P = .003, and for surgery/TACE HR of 0.4 (0.18;0.78); P = .009. CONCLUSION: Although early recurrence was associated with worse outcome, even in this population, systemic or locoregional treatments were associated with better PRS.

Telemedicine Improves Access to Hepatology Consultation with High Patient Satisfaction.

AIMS: Telemedicine between health care providers could be useful for improving the access to hepatology consultations, which is challenging in some regions. The primary objective of this study was to estimate the proportion of consultations that were resolved through a telemedicine program. Additionally, we evaluated patient satisfaction with this strategy. METHODS: Consecutive telemedicine consultations made by non-hepatologist health care providers from different regions of Argentina to a specialty hepatology team were included. Participants and hepatologists used e-mail, teleconference systems, WhatsApp, or telephone to interact, depending on their preferences. Consultations were considered to be resolved through telemedicine when a diagnosis and an adequate follow-up were achieved without the need to refer the patient to a hepatologist or other specialist. Patient satisfaction with telemedicine was evaluated using the Patient Satisfaction Questionnaire Short Form and Telemedicine Satisfaction Questionnaire. RESULTS: A total of 200 telemedicine consultations made by 24 physicians from 10 different provinces of Argentina were evaluated, of which 145 (73%; 95% CI: 66%-79%) were resolved through telemedicine. Practitioners specialities were as follows: family physicians, internists, gastroenterologists, infectious diseases, and obstetrics. The most frequent final diagnoses for those patients whose consultation was resolved through telemedicine were non-alcoholic fatty liver disease, viral hepatitis, and benign hepatic lesions. A high degree of patient satisfaction with telemedicine was observed in both questionnaires. CONCLUSIONS: Our results show the effectiveness of telemedicine in hepatology, with high resolution rate of consultations and rapid access to experts' assessment. Additionally, a high degree of patient satisfaction was observed using prevalidated questionnaires.

Latin American Association for the study of the liver (ALEH) practice guidance for the diagnosis and treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) currently represents an epidemic worldwide. NAFLD is the most frequently diagnosed chronic liver disease, affecting 20-30% of the general population. Furthermore, its prevalence is predicted to increase exponentially in the next decades, concomitantly with the global epidemic of obesity, type 2 diabetes mellitus (T2DM), and sedentary lifestyle. NAFLD is a clinical syndrome that encompasses a wide spectrum of associated diseases and hepatic complications such as hepatocellular carcinoma (HCC). Moreover, this disease is believed to become the main indication for liver transplantation in the near future. Since NAFLD management represents a growing challenge for primary care physicians, the Asociación Latinoamericana para el Estudio del Hígado (ALEH) has decided to organize this Practice Guidance for the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease, written by Latin-American specialists in different clinical areas, and destined to general practitioners, internal medicine specialists, endocrinologists, diabetologists, gastroenterologists, and hepatologists. The main purpose of this document is to improve patient care and awareness of NAFLD. The information provided in this guidance may also be useful in assisting stakeholders in the decision-making process related to NAFLD. Since new evidence is constantly emerging on different aspects of the disease, updates to this guideline will be required in future.

Diagnostic performance of three non-invasive fibrosis scores (Hepamet, FIB-4, NAFLD fibrosis score) in NAFLD patients from a mixed Latin American population.

INTRODUCTION AND AIMS: Several non-invasive scoring systems have been developed and validated worldwide to predict the risk of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). However, information about the performance of these systems in Latin American populations is scarce. Our aim was to evaluate the performance of the Hepamet Fibrosis Score, Fibrosis-4 (FIB-4) and the NAFLD Fibrosis Score (NFS) in a mixed Latin American group of NAFLD patients. METHODS: Clinical, laboratory and liver biopsy data collected from 379 biopsy-proven NAFLD patients from Latin American tertiary health centers were reviewed. Histological fibrosis stages were classified using the Kleiner score. Accuracy was determined, and new fibrosis score thresholds were calculated to better compare the performances of non-invasive tests and to explore their usefulness in excluding fibrosis. RESULTS: The distribution of fibrosis stages among the sample population was as follows: F0 (45%), F1 (27%), F2 (8%), F3 (16%) and F4 (4%). Using modified thresholds, the areas under the ROC curves (AUROC) for Hepamet and FIB-4 (0.73 and 0.74, respectively) to detect significant fibrosis were higher than that of NFS (0.58). However, the AUROCs of the three scores were not significantly different in advanced fibrosis and cirrhosis. To exclude fibrosis, we calculated lower cutoffs than standard thresholds for Hepamet, FIB-4 and NFS with similar performances. CONCLUSION: Thresholds of non-invasive fibrosis scores (Hepamet, FIB-4 and NFS) can be modified to maximize diagnostic accuracy in Latin American patients with NAFLD.

Argentinian clinical practice guideline for surveillance, diagnosis, staging and treatment of hepatocellular carcinoma.

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.

Cystatin C and Sarcopenia Predict Acute on Chronic Liver Failure Development and Mortality in Patients on the Liver Transplant Waiting List.

BACKGROUND: Cystatin C (CysC) is an early biomarker of renal dysfunction scarcely studied in patients awaiting liver transplantation (LT). Sarcopenia is frequent in cirrhosis and impacts prognosis. We aimed to assess the capability of these factors to predict survival and acute-on-chronic liver failure (ACLF) in patients awaiting LT, as well as early post-LT outcomes. METHODS: Single-center study that included all cirrhotic patients listed for LT between 2014 and 2017. Competing risk regression analysis was used to evaluate the capability of liver-, kidney-, and global status-related variables at waitlist (WL) inclusion to predict WL mortality and ACLF. Variables associated with post-LT outcomes were evaluated with logistic regression analysis. RESULTS: One-hundred-and-eighty patients were included. Fifty-six (31%) patients developed ACLF, 54 (30%) underwent LT and 35 (19%) died. In the adjusted competing risk regression analysis, CysC ≥ 1.5 mg/L, sarcopenia and MELD-Na were independent predictors of ACLF in the WL, while CysC ≥ 1.5 mg/L, sarcopenia and albumin were independent predictors of mortality. The cumulative incidence of ACLF and mortality at 12 months were 50% and 34% in patients with sarcopenia and CysC ≥1.5 mg/L. An estimated glomerular filtration rate by chronic kidney disease (CKD)-EPI-CysC-creatinine <60 mL/min/1.73 m at WL inclusion was an independent predictor of the need for renal replacement therapy (RRT) in the first month post-LT. CONCLUSIONS: Higher levels of CysC and sarcopenia are strongly associated with the ACLF and mortality in WL. The assessment of both risk factors may improve the prognostic evaluation and allow identifying a group of patients with a very high risk of poor outcomes while awaiting LT.