Liver transplantation in Latin America: reality and challenges.

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.

Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America.

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

Low hepatic artery resistive index on Doppler ultrasound performed on the first post-liver transplant day is associated both with hepatic artery thrombosis and decreased graft survival.

PURPOSE: Although liver transplantation (LT) outcomes have improved significantly over the last decades, early vascular complications are still associated with elevated risks of graft failure. Doppler ultrasound (DUS) enables detection of vascular complications, provides hepatic artery Resistive Index (RI). The aim of our study was to evaluate the association of the RI parameters of DUS performed in the first post-transplant week with post-transplant outcomes. METHODS: All consecutive patients undergoing a first LT between 2001 and 2019 at a single center were included. Patients were divided into two groups: RI < 0.55 and RI ≥ 0.55. Patients were also divided according to the presence or absence of hepatic artery thrombosis (HAT). Graft survival was compared between groups. RESULTS: Overall, 338 patients were included. HAT occurred in 23 patients (6.8%), of which 7 were partial and 16, complete. Biliary complications were more common in patients with HAT (10 [43.5%]) vs. 38 [12.1%] [p < 0.001]). Graft survival was lower for patients with HAT (p = 0.047). Also, RI < 0.55 was associated with increased incidence of HAT (p < 0.001). Additionally, patients with RI < 0.55 on post-operative day 1 had decreased graft survival as compared to patients with RI > 0.55 (p = 0.041). RI on post-operative day 3 and 5 was not predictive of inferior graft outcomes. CONCLUSIONS: Intensive use of DUS in the early post-LT period offers the possibility of early diagnosis of vascular complications, guiding medical and surgical management of HAT. Additionally, according to our data, low RI (< 0.55) on the first postoperative day also is a predictor of HAT and decreased graft-survival.

Percutaneous ethanol injection is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation.

PURPOSE: Locoregional therapies (LRT) are employed for bridging patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT). Although the main LRT options include transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) is an alternative with considerably lower costs. This study is a pioneering evaluation of the natural history of PEI bridging to OLT as compared to TACE. METHODS: All consecutive cirrhotic patients with HCC enlisted for OLT (2011-2020) at a single center were analyzed. Patients were divided into three LRT modality groups: PEI, TACE, and PEI+TACE. The primary study outcome was waitlist dropout due to tumor progression beyond Milan criteria. A comparison of post-transplant outcomes of patients as stratified by LRT modality also was performed. RESULTS: One hundred twenty-nine patients were included (PEI=56, TACE=43, PEI+TACE=30). The dropout rate due to tumor progression was not different among the three groups: PEI=8.9%, TACE=14%, PEI+TACE=16.7% (p=0.54). Thirteen (76.4%) patients underwent OLT after successful downstaging (3 [75%] in the PEI group, 5 [83.3%] in the TACE group, and 5 [71.4%] in the PEI+TACE group). For the 96 patients undergoing OLT, 5-year post-transplant recurrence-free survival was PEI=55.6% vs. TACE=55.1% vs. PEI+TACE=71.4% (p=0.42). Complete/near-complete pathological response rate was similar among groups (p=0.82). CONCLUSION: Dropout rates and post-transplant recurrence-free survivals related to PEI were comparable to those of TACE. This study supports the use of PEI alone or in combination with TACE for HCC patients awaiting OLT whenever RFA is not an option.

Interaction of Microbiome, Diet, and Hospitalizations Between Brazilian and American Patients With Cirrhosis.

BACKGROUND & AIMS: Gut microbiota are affected by diet, country, and affect outcomes in cirrhosis. Western diets are associated with dysbiosis. Comparisons with other diets is needed. We aimed to compare cirrhosis patients from the United States with cirrhosis patients from Brazil with respect to diet, microbiota, and impact on hospitalizations. METHODS: Healthy controls and compensated/decompensated outpatients with cirrhosis from the United States and Brazil underwent dietary recall and stool for 16S ribosomal RNA sequencing. Demographics and medications/cirrhosis details were compared within and between countries. Patients with cirrhosis were followed up for 90-day hospitalizations. Regression for Shannon diversity was performed within cirrhosis. Regression for hospitalizations adjusting for clinical and microbial variables was performed. RESULTS: Model for end-stage liver disease (MELD), diabetes, ascites, and albumin were similar, but more Americans were men, had higher hepatic encephalopathy and alcohol/hepatitis C etiology, with lower nonalcoholic fatty liver disease than Brazilians. Brazilians had higher cereal, rice, and yogurt intake vs the United States. As disease progressed, cereals, rice/beans, coffee, and chocolate consumption was reduced. Microbial diversity was higher in Brazilians. Within cirrhosis, high diversity was related to Brazilian origin (P < .0001), age, and cereal intake (P = .05), while high MELD scores (P = .009) and ascites (P = .05) did the reverse. Regardless of stage, beneficial taxa and taxa associated with grant and yogurt intake were higher (Ruminococcaceae, Christensenellacae, and Prevotellaceae), while pathobionts (Porphyromonadaceae, Sutterellaceae, and Enterobacteriaceae) were lower in Brazilians. More Americans were hospitalized vs Brazilians (P = .002). On regression, MELD (P = .001) and ascites (P = .001) were associated with higher hospitalizations, while chocolate (P = .03) and Brazilian origin (P = .001) were associated with lower hospitalizations with/without microbiota inclusion. CONCLUSIONS: Brazilian cirrhotic patients follow a diet richer in cereals and yogurt, which is associated with higher microbial diversity and beneficial microbiota and could contribute toward lower hospitalizations compared with a Western-diet-consuming American cohort.

Evaluation of the genetic toxicity of sofosbuvir and simeprevir with and without ribavirin in a human-derived liver cell line.

Direct-acting antivirals have revolutionized the treatment of chronic hepatitis C. Sofosbuvir and simeprevir are prescribed worldwide. However, there is a scarcity of information regarding their genotoxicity. Therefore, the present study assessed the cytotoxic and genotoxic effects of sofosbuvir and simeprevir, alone and combined with ribavirin. HepG2 cells were analyzed using the in vitro cytokinesis-block micronucleus cytome assay. Cells were treated for 24 h with sofosbuvir (0.011-1.511 mM), simeprevir (0.156-5.0 µM), and their combinations with ribavirin (0.250-4.0 mM). No significant differences were observed in the nuclear division cytotoxicity index, reflecting the absence of cytotoxic effects associated to sofosbuvir. However, the highest concentration of simeprevir showed a significant difference for the nuclear division cytotoxicity index. Moreover, significant results were observed for nuclear division cytotoxicity index in two combinations of sofosbuvir plus ribavirin and only in the highest combination of simeprevir plus ribavirin. Additionally, our results showed that sofosbuvir did not increase the frequency of chromosomal damage, but simeprevir significantly increased the frequency of micronuclei at the highest concentrations. The combination index demonstrated that both sofosbuvir and simeprevir produced antagonism to the genotoxic effects of ribavirin. In conclusion, our results showed that simeprevir, but not sofosbuvir, has genotoxic effects in HepG2 cells.

Impact of intraoperative blood salvage and autologous transfusion during liver transplantation for hepatocellular carcinoma.

PURPOSE: Intraoperative blood salvage (IBS) with autologous blood transfusion is controversial in liver transplantation (LT) for hepatocellular carcinoma (HCC). This study evaluated the role of IBS usage in LT for HCC. METHODS: In a retrospective cohort study at a single center from 2002 to 2018, the outcomes of LT surgery for HCC were analyzed. Overall survival and disease-free survival of patients who received IBS were compared with those who did not receive IBS. Cancer recurrence, length of hospital stay, post-transplant complications, and blood loss also were evaluated. The primary aim of this study was to evaluate overall mid-term and long-term survival (4 and 6 years, respectively). RESULTS: Of the total 163 patients who underwent LT for HCC in the study period, 156 had complete demographic and clinical data and were included in the study. IBS was used in 122 and not used in 34 patients. Ninety-five (60.9%) patients were men, and the mean patient age was 58.5 ± 7.6 years. The overall 1-year, 5-year, and 7-year survival in the IBS group was 84.2%, 67.7%, and 56.8% vs. 85.3%, 67.5%, and 67.5% in the non-IBS group (p = 0.77). The 1-year, 5-year, and 7-year disease-free survival in the IBS group was 81.6%, 66.5%, and 55.4% vs. 85.3%, 64.1%, and 64.1% in the non-IBS group (p = 0.74). For patients without complete HCC necrosis (n = 121), the 1-year, 5-year, and 7-year overall survival rates for those who received IBS (n = 95) were 86.2%, 67.7%, and 49.6% vs. 84.6%, 70.0%, and 70.0% for 26 patients without IBS (p = 0.857). For the same patients, the 1-year, 5-year, and 7-year disease-free survival in the IBS group was 84.0%, 66.8%, and 64.0% vs. 88.0%, 72.8%, and 72.8% in the non-IBS group (p = 0.690). CONCLUSION: IBS does not appear to be associated with worse outcomes in patients undergoing LT for HCC, even in the presence of viable HCC in the explant. There seems to be no reason to contraindicate the use of IBS in LT for HCC.

MELD EXCEPTION POINTS PROVIDE AN ENOURMOUS ADVANTAGE FOR RECEIVING A LIVER TRANSPLANT IN BRAZIL.

BACKGROUND: Current policy for listing to liver transplant (LT) may place cirrhotic patients without MELD exception points (CIR) in a disadvantageous position if compared to patients enlisted with appealed MELD scores - patients with hepatocellular carcinoma (HCC) or special conditions other than hepatocellular carcinoma (SPE). Transplant rates, delisting, and waitlist mortality of CIR, HCC, and SPE candidates were compared. OBJECTIVE: The aim of this study is to counterweight the listing rate and speed of listing of HCC, SPE, and CIR patients. To the best of our knowledge, this is the first study comparing the outcomes of patients enlisted for SPE to those of HCC and CIR. In several countries worldwide, SPE patients also receive appealed MELD scores in a similar way of HCC patients. METHODS: Two cohorts of patients listed for LT in a single institution were evaluated. The first cohort (C1, n=180) included all patients enlisted on August 1st, 2008, and all additional patients listed from this date until July 31st, 2009. The second cohort (C2, n=109) included all patients present on the LT list on October 1st, 2012, and all additional patients listed from this date until May 2014. RESULTS: In both cohorts, HCC patients had a higher chance of receiving a LT than CIR patients (C1HR =2.05, 95%CI=1.54-2.72, P<0.0001; C2HR =3.17, 95%CI =1.83-5.52, P<0.0001). For C1, 1-year waiting list mortality was 21.6% (30.0% for CIR vs 9.5% for HCC vs 7.1% for SPE) (P<0.001). For C2, 1-year waiting list mortality was 13.3% (25.7% for CIR, 8.3% for HCC, and 4.0% for SPE) (P<0.001). Post-transplant survival was similar among the three groups. CONCLUSION: Compared to CIR, SPE and HCC patients had lower wait list mortality. CIR patients had the highest waitlist mortality and the lowest odd of LT. Current LT allocation system does not allow equitable organ allocation.

Os critérios especiais de pontuação MELD proporcionam uma enorme vantagem a pacientes listados para transplante de fígado no Brasil / Meld exception points provide an enourmous advantage for receiving a liver transplant in brazil

ABSTRACT BACKGROUND: Current policy for listing to liver transplant (LT) may place cirrhotic patients without MELD exception points (CIR) in a disadvantageous position if compared to patients enlisted with appealed MELD scores - patients with hepatocellular carcinoma (HCC) or special conditions other than hepatocellular carcinoma (SPE). Transplant rates, delisting, and waitlist mortality of CIR, HCC, and SPE candidates were compared. OBJECTIVE: The aim of this study is to counterweight the listing rate and speed of listing of HCC, SPE, and CIR patients. To the best of our knowledge, this is the first study comparing the outcomes of patients enlisted for SPE to those of HCC and CIR. In several countries worldwide, SPE patients also receive appealed MELD scores in a similar way of HCC patients. METHODS: Two cohorts of patients listed for LT in a single institution were evaluated. The first cohort (C1, n=180) included all patients enlisted on August 1st, 2008, and all additional patients listed from this date until July 31st, 2009. The second cohort (C2, n=109) included all patients present on the LT list on October 1st, 2012, and all additional patients listed from this date until May 2014. RESULTS: In both cohorts, HCC patients had a higher chance of receiving a LT than CIR patients (C1HR =2.05, 95%CI=1.54-2.72, P<0.0001; C2HR =3.17, 95%CI =1.83-5.52, P<0.0001). For C1, 1-year waiting list mortality was 21.6% (30.0% for CIR vs 9.5% for HCC vs 7.1% for SPE) (P<0.001). For C2, 1-year waiting list mortality was 13.3% (25.7% for CIR, 8.3% for HCC, and 4.0% for SPE) (P<0.001). Post-transplant survival was similar among the three groups. CONCLUSION: Compared to CIR, SPE and HCC patients had lower wait list mortality. CIR patients had the highest waitlist mortality and the lowest odd of LT. Current LT allocation system does not allow equitable organ allocation.

RESUMO CONTEXTO: É possível que política atual de inclusão no transplante de fígado (LT) esteja colocando os pacientes cirróticos sem pontos de exceção MELD (CIR) em uma posição desvantajosa se comparados aos pacientes listados com escores de critério especial MELD - pacientes com carcinoma hepatocelular (HCC) ou outras condições especiais (SPE). As taxas de transplante, exclusão e mortalidade de lista de espera de candidatos com CIR, HCC e SPE foram comparadas. OBJETIVO: O objetivo deste estudo é comparar a taxa de listagem e também a velocidade de listagem de pacientes listados pelas três possíveis categorias de listagem no Brasil (HCC, SPE e CIR). Há muito poucos estudos prévios comparando os desfechos de pacientes listados por SPE ao desfecho de pacientes com HCC e também ao desfecho de pacientes não priorizados (CIR). Em muitos países, pacientes listados para transplante de fígado com SPE são priorizados para transplante em um modo similar ao que ocorre com pacientes com HCC. MÉTODOS: Foram avaliadas duas coortes de pacientes listados para LT em uma única instituição. A primeira coorte (C1, n=180) incluiu todos os pacientes listados em 1º de agosto de 2008 e todos os pacientes adicionais listados dessa data até 31 de julho de 2009. A segunda coorte (C2, n=109) incluiu todos os pacientes presentes na LT em 1º de outubro de 2012 e todos os pacientes listados dessa data até maio de 2014. RESULTADOS: Em ambas as coortes, os pacientes com CHC tiveram uma chance maior de receber uma LT do que os pacientes com CIR (C1HR =2,05, CI95% =1,54-2,72, P<0,0001; C2HR =3,17, CI95% =1,83-5,52, P<0,0001). Para C1, a mortalidade na lista de espera em um ano foi de 21,6% (30,0% para CIR vs 9,5% para HCC vs 7,1% para SPE) (P<0,001). Para C2, a mortalidade na lista de espera em um ano foi de 13,3% (25,7% para CIR, 8,3% para HCC e 4,0% para SPE) (P<0,001). A sobrevida pós-transplante foi semelhante entre os três grupos. CONCLUSÃO: Comparados aos pacientes CIR, os pacientes SPE e HCC, apresentaram menor mortalidade na lista de espera. Os pacientes com CIR tiveram a maior mortalidade na lista de espera e a menor probabilidade de LT. O atual sistema de alocação de LT não permite alocação equitativa de órgãos.

Exposure to organic solvents and hepatotoxicity.

The purpose of this study was to identify the long-term effect of chemical exposure on the liver. Laboratory tests included alanine aminotransferase (ALT) dosage and oxidative stress tests, such as thiobarbituric acid reactive substances in plasma and superoxide dismutase (SOD) and glutathione S-transferase analysis in erythrocytes. The cross-sectional study comprised 70 workers, 30 of them exposed to organic solvents and 40 not exposed. All those exposed presented at least 5 years of exposure to solvents. Hepatitis B and C, known hepatic disease, comorbidities, use of alcohol, illicit drugs or hepatotoxic medications, smoking, body mass index >30, female sex and age (<18 or >65) were excluded from the sample. Results indicated that elevated ALT was more frequent in the exposed group compared to controls: 33% vs. 10.5%, with a statistical significance (p < 0.05). Thiobarbituric acid reactive substances were significantly elevated (p < 0.01) in the exposed group in comparison to controls. Antioxidant enzymes were more elevated in the exposed group compared to controls: SOD 7.29 (4.30-8.91) USOD/mg of protein vs. 3.48 (2.98-5.28) USOD/mg of protein and GST 2.57 µmol/min/mg of protein (1.80-4.78) vs. 1.81 µmol/min/mg of protein (1.45- 2.30) µM/min/mg of protein. The results suggest an association between exposure to organic solvents and hepatotoxicity.

Hepatocellular carcinoma in non-alcoholic fatty liver disease (NAFLD) - pathological evidence for a predominance of steatohepatitic inflammatory non-proliferative subtype.

OBJECTIVES: This study evaluated clinical and pathological aspects of patients with hepatocellular carcinoma (HCC) secondary to non-alcoholic fatty liver disease (NAFLD) and related these factors to immunohistochemical markers representative of the proliferative class. METHODS: We evaluated 35 HCC nodules from 21 patients diagnosed with NAFLD undergoing liver resection (n=12) or liver transplantation (n=8) or both (n=1). Demographic, clinical and biochemical data were compared to histological features and to immunohistochemical reactivity for K19 and Ki-67. RESULTS: Cirrhosis was present in 58% of patients. Ages ranged from 50 to 77 years. Sixteen patients (76%) were male and had type 2 diabetes mellitus, 81% had arterial hypertension, and 90% had BMI above 25 kg/m². Alpha-fetoprotein levels were normal in 62% of patients. Twenty-five (70%) nodules were diagnosed as "steatohepatitic HCC". Only 32% of the nodules presented high levels of Ki-67 (>10%) and/or K19 (>5%), although 63% were poorly differentiated (G.3/G.4) according to Edmondson & Steiner grading system. K19 positivity (>5%) was associated with higher degree of intratumoral inflammation (G.2/G.3), and with fibrosis, both at the center of the tumor and at the tumor front, whereas Ki-67 positivity (>10%) was associated with ballooning of neoplastic cells and occurred in more than 70% in non-cirrhotic patients. CONCLUSION: NAFLD-related HCC was found in non-cirrhotic patients in 42% of cases, alpha-fetoprotein level was normal in 63% and "steatohepatitic HCC" was the predominant histological type. Immunoexpression of K19 and/or Ki-67 occurred in 32% of the nodules and were associated with intratumoral inflammation and ballooning, suggesting that HCC in MtS may be preferentially "an inflammatory, non-proliferative subtype of HCC".

High Prevalence of Multidrug Resistant Bacteria in Cirrhotic Patients with Spontaneous Bacterial Peritonitis: Is It Time to Change the Standard Antimicrobial Approach?

Introduction: Spontaneous bacterial peritonitis (SBP) has a deleterious clinical impact in end-stage liver disease, and multidrug resistance has increased, raising concern about effectiveness of traditional antibiotic regimens. Patients and Methods: Single-center retrospective study of ascitic fluid infections in cirrhotic patients. Results: We analyzed medical records related to 2129 culture-positive ascitic fluid and found 183 samples from cirrhotic patients. There were 113 monobacterial SBP cases from 97 cirrhotic patients; 57% of patients were male; hepatitis C and alcohol were the main etiologies for cirrhosis. Multidrug resistant bacteria were isolated in 46.9% of SBP samples, and third-generation cephalosporin and quinolone resistant reached 38.9% and 25.7% of SBP cases. Conclusion: SBP due to multidrug resistant bacteria is a growing problem, and one should consider reported resistance profiles for the decision-making process of empirical first-line treatment prescription.

Sofosbuvir-based antiviral therapy in patients with recurrent HCV infection after liver transplant: A real-life experience.

INTRODUCTION AND AIM: Recurrent HCV infection after liver transplant (LT) has a negative impact on graft and patient survival. The aim of this study is to describe the efficacy and safety of sofosbuvir (SOF-based) regimens in the treatment of recurrent HCV after liver transplant (LT). MATERIALS AND METHODS: This retrospective study included 68 adults with recurrent HCV infection after LT, treated with different SOF-based regimens between March 2015 and December 2016. The choice of regimens, their duration and use of ribavirin (RBV) was made by the treating physician. The efficacy of antiviral treatment was assessed based on the sustained viral response obtained 12 weeks after the end of treatment (SVR12), according to an intention-to-treat analysis. RESULTS: The most frequent HCV genotypes were 1 and 3 (n=35, 51.4% and n=31, 45.6%, respectively). Only 22 patients were treatment naïve (32.3%) and 7 had cirrhosis (10.2%). SOF+daclatasvir (DCV) was the most commonly used regimen (n=63, 92.6%). Most patients used RBV (n=56, 82.3%) and were treated for 12 weeks (n=66, 97%). Overall SVR12 was 95.5% (65/68 patients). Three patients had virologic failure. Three patients had serious adverse events, however, no one discontinued treatment prematurely. RBV-related anaemia was the most frequent adverse event (n=34, 50%). Four patients had severe cellular graft rejection after HCV elimination, while immunosuppression remained stable. CONCLUSION: SOF-based therapy is highly effective and safe to treat HCV recurrence after LT. Cellular graft rejection following the successful treatment of HCV needs further investigation.

How are HCV-infected patients being identified in Brazil: a multicenter study.

BACKGROUND: Hepatitis C is an important health problem. In Brazil, 1-2 million people are infected. Despite this expressive number, and the availability of very successful treatment, many patients remained undiagnosed mainly because of the asymptomatic nature of the infection. OBJECTIVES: To describe epidemiological characteristics of HCV-infected patients seen at referral centers in Brazil, the source of referral, and the time spanned to reach a reference center, in order to improve the identification of undiagnosed patients. METHODS: Multicenter observational, cross-sectional study carried out in 15 centers of Brazil, between January/2016 and June/2017. Data of patients with a confirmed diagnosis (anti-HCV and HCV-RNA) were collected by interview using standard questionnaires and by review of charts. RESULTS: Two thousand patients were included; 55.1% were male, mean age 58±11 years. Only 14.9% had higher education and 84.2% received up to five monthly minimum Brazilian wages (approximately US$260.00/month). The time between diagnosis and beginning of follow-up was 22.9 months. The most common reasons for testing were check-up (33.2%) and blood donation (19%). General practitioners diagnosed most of the patients (30.1%). Fibrosis stage was mainly evaluated by liver biopsy (61.5%) and 31.3% of the patients were cirrhotic at diagnosis. CONCLUSIONS: This multicenter Brazilian study showed that the mean time to reach a referral center for treatment was almost two years. Primary care physicians diagnoses most hepatitis C cases in the country. Population campaigns and medical education should be encouraged to intensify screening of asymptomatic individuals, considering the efficiency of check-ups in identifying new patients.

BCLC-B Subclassification and the Hong Kong Liver Cancer System in Intermediate Hepatocellular Carcinoma: Identifying Candidates for Curative Therapy.

INTRODUCTION: The intermediate stage of the Barcelona Clinic Liver Cancer (BCLC) classification includes a heterogenous population of patients with hepatocellular carcinoma (HCC), and palliative treatment with transarterial chemoembolization is recommended for all of them. In this regard, 2 other classifications could be useful, the subclassification BCLC-B (SUB) and the classification Hong Kong Liver Cancer (HKLC). OBJECTIVE: To determine the indication of curative or palliative treatment between SUB and HKLC in BCLC-B patients. PATIENTS AND METHODS: A retrospective study in HCC patients seen between 2011 and 2016 in southern Brazil. Demographic, clinical, and laboratory data were collected. HCC staging was performed with BCLC, SUB, and HKLC. RESULTS: A total of 570 patients with HCC were assessed, of whom 95 were classified as BCLC-B: 25 (26.0%) B1, 48 (50.5%) B2, 9 (9.5%) B3, and 13 (13.7%) B4. Overall median survival was 21.1 (95% confidence interval, 14.2-28.0) months. Median survival was higher for BCLC-B1 patients than in subgroups B3 (P=0.046) and B4 (P=0.001), and this was also seen for B2 versus B4 (P=0.044). Regarding the HKLC classification, a significantly higher median survival was observed for HKLC-I and HKLC-IIB in relation to the categories HKLC-IIIA (P<0.001 and 0.004, respectively) and HKLC-IIIB (P<0.001 and 0.006, respectively). When HKLC was applied, the following were identified as candidates for curative treatment: BCLC-B1, 24 (96.0%); BCLC-B2, 26 (54.2%); BCLC-B3, 0 (0%); and BCLC-B4, 3 (23.1%). CONCLUSION: In intermediate HCC, SUB was able to identify a subset of patients with a higher overall survival. According to HKLC, 55.8% of BCLC-B patients could receive curative treatment.

Pre-transplant ALBI Grade 3 Is Associated with Increased Mortality After Liver Transplantation.

BACKGROUND: Although MELD score is a reliable tool for estimating mortality in the waiting list, criteria for preoperative prediction of survival after liver transplantation (LT) are lacking. ALBI score was validated as a prognostic marker for hepatocellular carcinoma patients undergoing transarterial chemoembolization, hepatic resection, and sorafenib treatment but not for LT outcomes yet. This study aimed to evaluate ALBI score as a prognostic factor in LT. METHODS: This is a single-center analysis of patients undergoing LT between October 2001 and June 2017. Primary endpoint was overall post-LT mortality. Secondary endpoint was 90-day mortality. RESULTS: Of all 301 patients included in this study, 185 (61.5%) were males. The median age was 54.1 ± 11.3 years. Univariate and multivariate analysis revealed that ALBI grade 3 (HR 1.836, 95% CI 1.154-2.921, p = 0.010), low serum albumin (HR 0.628, 95% CI 0.441-0.893, p = 0.010), black race (HR 2.431, 95% CI 1.160-5.092, p = 0.019), and elevated body mass index (HR 1.061, 95% CI 1.022-1.102, p = 0.002) all were associated with decreased overall survival following LT. Patients with both ALBI grade 3 (n = 25) and calculated MELD score ≥ 25 had the lowest overall survival (p < 0.001). DISCUSSION: ALBI grade 3 was related to lower post-LT survival and can be utilized as a tool for risk stratification in LT.

How are HCV-infected patients being identified in Brazil: a multicenter study

ABSTRACT Background: Hepatitis C is an important health problem. In Brazil, 1-2 million people are infected. Despite this expressive number, and the availability of very successful treatment, many patients remained undiagnosed mainly because of the asymptomatic nature of the infection. Objectives: To describe epidemiological characteristics of HCV-infected patients seen at referral centers in Brazil, the source of referral, and the time spanned to reach a reference center, in order to improve the identification of undiagnosed patients. Methods: Multicenter observational, cross-sectional study carried out in 15 centers of Brazil, between January/2016 and June/2017. Data of patients with a confirmed diagnosis (anti-HCV and HCV-RNA) were collected by interview using standard questionnaires and by review of charts. Results: Two thousand patients were included; 55.1% were male, mean age 58 ± 11 years. Only 14.9% had higher education and 84.2% received up to five monthly minimum Brazilian wages (approximately US$260.00/month). The time between diagnosis and beginning of follow-up was 22.9 months. The most common reasons for testing were check-up (33.2%) and blood donation (19%). General practitioners diagnosed most of the patients (30.1%). Fibrosis stage was mainly evaluated by liver biopsy (61.5%) and 31.3% of the patients were cirrhotic at diagnosis. Conclusions: This multicenter Brazilian study showed that the mean time to reach a referral center for treatment was almost two years. Primary care physicians diagnoses most hepatitis C cases in the country. Population campaigns and medical education should be encouraged to intensify screening of asymptomatic individuals, considering the efficiency of check-ups in identifying new patients.

Serum Factor V Is a Continuous Biomarker of Graft Dysfunction and a Predictor of Graft Loss After Liver Transplantation.

BACKGROUND: Factor V has never been compared to a validated early allograft dysfunction (EAD) definition. We aimed to assess factor V as a biomarker of EAD and a predictor of graft loss after liver transplantation (LT). METHODS: We retrospectively assessed the serum factor V levels on postoperative day 1 after LT. Patients were divided according to their factor V levels into the ≤36.1 U/mL and > 36.1 U/mL groups. The primary outcome was graft loss within 1, 3, and 6 months. The secondary outcome was EAD, as defined by Olthoff et al. Predictors of outcomes were identified by multivariable logistic regression. RESULTS: Two hundred twenty-seven patients were included in the study: 74 with factor V of 36.1 U/mL or less and 153 with factor V >36.1 U/mL. EAD was diagnosed in 41 (55.4%) of 74 patients with factor V of 36.1 U/mL or less and in 20/153 (13.1%) patients with factor V >36.1 U/mL (P < 0.001). According to the multivariable regression model, factor V was a continuous marker of EAD (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.94-0.98 per U/mL). Among the study groups, the 1-, 3-, and 6-month graft survival rates were 82%, 74%, and 74%, respectively, for patients with factor V of 36.1 U/mL or less and 98%, 95%, and 95%, respectively, for patients with factor V >36.1 U/mL (P = 0.001). Factor V was a continuous predictor for 3- and 6-month graft losses (OR, 0.96; 95% CI, 0.94-0.99 and OR, 0.97; 95% CI, 0.94-0.99 per U/mL), whereas EAD was not significant when adjusted for factor V. CONCLUSION: Factor V is an early marker for EAD and is a continuous predictor of short-term graft loss after LT.