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.

Influence of Tacrolimus Intrapatient Variability on Allograft Rejection Frequency and Survival Following Liver Transplantation.

BACKGROUND: Tacrolimus is the primary calcineurin inhibitor used in immunosuppressive regimens to prevent allograft rejection (AR) after organ transplantation. Recent studies have linked intrapatient variability (IPV) of tacrolimus with AR occurrence and reduced survival, especially in kidney transplant recipients. However, limited data are available on the impact of tacrolimus IPV on adverse outcomes after liver transplantation (LT). AIMS: The aim of this study was to assess the association between tacrolimus IPV using various methodologies with acute AR and long-term patient survival after LT. METHODS: All patients who underwent LT from January 2010 to July 2021 were retrospectively evaluated. Tacrolimus IPV was calculated for each patient using the mean and SD, mean absolute deviation (MAD), coefficient of variation (CV), and time in therapeutic range (TTR). These measures were then compared with AR within the first 24 months after LT and to long-term survival. RESULTS: Out of 234 patients, 32 (13.7%) developed AR and 183 (78.2%) survived, with a mean follow-up of 101 ± 43 months. Tacrolimus IPV, assessed by mean, SD, MAD, and CV, was 8.3 ± 2.1, 2.7 ± 1.3, 32.0% ± 11.7%, and 39.4% ± 15.4%, respectively. There was no statistically significant correlation between Tacrolimus IPV and AR or survival post-LT. CONCLUSIONS: In a large cohort of patients from diverse racial backgrounds, tacrolimus IPV was not associated with clinically relevant outcomes such as AR and survival after LT.

Retrieval of HCV patients lost to follow-up as a strategy for Hepatitis C Microelimination: results of a Brazilian multicentre study.

BACKGROUND: Several HCV patients in Brazil were lost to follow-up (LTFU) in the last two decades before achievement of sustained virological response (SVR). Strategies to recall those diagnosed but untreated patients have been used elsewhere with different success rates. AIM: To identify and retrieve LTFU patients in order to offer them the treatment with the current highly effective direct acting antiviral agents (DAAs). METHODS: Registries ofall HCV patients from three large reference centers in Brazil were retrospectively reviewed to identify those with no registry of SVR. Reasons for non-achievement of SVR were elicited in HCV-RNA + patients. All patients who were not treated or cured were contacted to offer the therapy with DAAs. RESULTS: 10,289 HCV patients (50% males, mean age 52 ± 11 years) were identified. Only 4,293 (41.7%) had been successfully treated previously. From the remaining 5,996 most were LTFU (59%), were not treated for other reasons (14.7%) or were non-responders (26.3%). After revision of the charts 3,559 were considered eligible to be retrieved. The callback success of phone calls was 18%, 13% to cellphone messages (SMS or WhatsApp) and 7% to regular mail. Five-hundred sixty patients had been already treatedor were on treatment and 234 were reported to be dead or transplanted. Finally, 201 had made an appointment and initiated antiviral treatment. CONCLUSION: Even considering the low callback rate, retrieval of LTFU patients was shown to be an important strategy forhepatitis C micro-elimination in Brazil.

Response to Ursodeoxycholic Acid May Be Assessed Earlier to Allow Second-Line Therapy in Patients with Unresponsive Primary Biliary Cholangitis.

BACKGROUND: Response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has been traditionally assessed 1 to 2 years after treatment initiation. With the development of new drugs, some patients may benefit from an earlier introduction of second-line therapies. AIMS: This study aims to identify whether well-validated response criteria could correctly identify individuals likely to benefit from add-on second-line therapy at 6 months. METHODS: Analysis of a multicenter retrospective cohort which included only patients with clear-cut PBC. RESULTS: 206 patients with PBC (96.6% women; mean age 54 ± 12 years) were included. Kappa concordance was substantial for Toronto (0.67), Rotterdam (0.65), Paris 1 (0.63) and 2 (0.63) criteria at 6 and 12 months, whereas Barcelona (0.47) and POISE trial (0.59) criteria exhibited moderate agreement. Non-response rates to UDCA was not statistically different when assessed either at 6 or 12 months using Toronto, Rotterdam or Paris 2 criteria. Those differences were even smaller or absent in those subjects with advanced PBC. Mean baseline alkaline phosphatase was 2.73 ± 1.95 times the upper limit of normal (× ULN) among responders versus 5.05 ± 3.08 × ULN in non-responders (p < 0.001). CONCLUSIONS: After 6 months of treatment with UDCA, the absence of response by different criteria could properly identify patients who could benefit from early addition of second-line therapies, especially in patients with advanced disease or high baseline liver enzymes levels.

Risk factors for cancer in patients with primary biliary cholangitis and autoimmune hepatitis and primary biliary cholangitis overlap syndrome.

INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) and PBC overlap syndrome (AIH/PBC) have been associated with a higher risk of hepatocellular carcinoma (HCC) and extra-hepatic malignancy (EHM). This study aims to assess potential risk factors associated with cancer development in PBC and AIH/PBC. MATERIALS AND METHODS: The Brazilian Cholestasis Study Group database was reviewed to compare clinical and laboratory features of PBC patients with HCC and EHM with those without cancer. RESULTS: Among the 752 PBC patients enrolled, 64 of them with AIH/PBC, 87 cancers were identified in 72 patients, including 20 cases of HCC and 67 of EHM. Patients with HCC had a higher prevalence of cirrhosis (95% vs. 32.5% of those subjects without cancer, p≤0.001), smoking (55% vs. 12.3%, p≤0.001), CREST syndrome (30% vs 7.6%, p=0.003) and prior azathioprine (30% vs 8%, p= 0.005) and prednisone (35% vs 14%, p= 0.018) use, whereas patients with EHM had a higher prevalence of smoking (42.3% vs 12.4% of those subjects without cancer, p= <0.001), AMA positivity (96.6% vs 80.1%, p≤0.001), azathioprine therapy (21% vs 7.9%, p= 0.01) and concurrent other autoimmune diseases. In multivariate analysis, cirrhosis, obesity and prior azathioprine therapy were independent risk factors for HCC, while Sjogren syndrome and psoriasis were associated with EHM. Fibrates reduced EHM risk. CONCLUSIONS: The prevalence of EHM is higher when compared to HCC in PBC patients. Cirrhosis, obesity, prior azathioprine use, and concurrent autoimmune diseases were significantly associated with cancer in PBC.

Telemonitoring of the Continuum of Care of Hepatitis C During the COVID-19 Pandemic in Brazil.

Introduction: To accomplish elimination of hepatitis C virus (HCV) by 2030, as proposed by the World Health Organization, the Brazilian Ministry of Health outlined the Hepatitis C Elimination Plan, which provides coverage of all critical steps in the continuum of care (CoC) of hepatitis C. As expected, the advent of COVID-19 pandemic has disrupted the CoC of hepatitis C worldwide. The Brazilian Liver Institute launched a remote patient monitoring (RPM) program to assist the general population at risk in HCV testing and to provide linkage and retention to care for HCV-positive subjects. The RPM program was also designed to relink HCV-positive patients lost to follow-up during the COVID-19 pandemic due to their limited access to the health care system. Methods: The HCV telemonitoring number was highly advertised in Brazilian media. The RPM program was conducted by dedicated health care personnel trained to follow a predefined script designed to provide awareness, ensure consistent information for educational purposes, and recruit eligible participants to be tested for HCV. Results: From August 2020 to December 2021, 3,738 subjects entered in contact with RPM. There were 26,884 interactions (mean 7.2 interactions per participant), mostly by WhatsApp (78%). Twenty out of those 221 subjects (9%) who tested were HCV positive. Those subjects altogether with 128 other patients with HCV, tested elsewhere, were followed in the HCV CoC. Up to now, 94% of them were linked to care, 24% are undergoing treatment and 8% achieved sustained virological response (SVR). Conclusions: Our preliminary results showed that HCV CoC telemonitoring was a feasible and useful strategy to follow HCV at-risk subjects through all cascade of care until SVR during the COVID-19 health care disruption. It could be used beyond the defervescence of SARS-CoV-2 pandemic to ensure linkage to care of those HCV-positive patients.

Anti-mitochondrial Antibody-Negative Primary Biliary Cholangitis Is Part of the Same Spectrum of Classical Primary Biliary Cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease in which anti-mitochondrial antibodies (AMA) are the diagnostic hallmark. Whether AMA-negative PBC patients represent a different phenotype of disease is highly debated. AIMS: The purpose of our study was to compare AMA-positive and AMA-negative PBC patients in a large non-white admixed Brazilian cohort. METHODS: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian PBC patients, stratifying data according to AMA status. RESULTS: A total of 464 subjects (95.4% females, mean age 56 ± 5 years) with PBC were included. Three hundred and eighty-four (83%) subjects were AMA-positive, whereas 80 (17%) had AMA-negative PBC. Subjects with AMA-negative PBC were significantly younger (52.2 ± 14 vs. 59.6 ± 11 years, p = 0.001) and had their first symptom at an earlier age (43.2 ± 13 vs. 49.5 ± 12 years, p = 0.005). Frequency of type 2 diabetes was significantly increased in subjects with AMA-negative PBC (22.5% vs. 12.2%, p = 0.03). Lower IgM (272.2 ± 183 vs. 383.2 ± 378 mg/dL, p = 0.01) and triglycerides (107.6 ± 59.8 vs.129.3 ± 75.7 mg/dL, p = 0.025) and higher bilirubin (3.8 ± 13.5 vs. 1.8 ± 3.4 mg/dL, p = 0.02) levels were also observed in this subgroup. Response to ursodeoxycholic acid varied from 40.5 to 63.3% in AMA-positive and 34 to 62.3% in AMA-negative individuals, according to different response criteria. Outcomes such as development of liver-related complications, death and requirement for liver transplantation were similar in both groups. CONCLUSIONS: AMA-negative PBC patients are similar to their AMA-positive counterparts with subtle differences observed in clinical and laboratory features.

Clinical features and treatment outcomes of primary biliary cholangitis in a highly admixed population.

INTRODUCTION AND OBJECTIVES: Little is known about primary biliary cholangitis (PBC) in non-whites. The purpose of this study was to evaluate clinical features and outcomes of PBC in a highly admixed population. MATERIAL AND METHODS: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian patients with PBC. RESULTS: 562 patients (95% females, mean age 51 ± 11 years) with PBC were included. Concurrent autoimmune diseases and overlap with autoimmune hepatitis (AIH) occurred, respectively, in 18.9% and 14%. After a mean follow-up was 6.2 ± 5.3 years, 32% had cirrhosis, 7% underwent liver transplantation and 3% died of liver-related causes. 96% were treated with ursodeoxycholic acid (UDCA) and 12% required add-on therapy with fibrates, either bezafibrate, fenofibrate or ciprofibrate. Response to UDCA and to UDCA/fibrates therapy varied from 39%-67% and 42-61%, respectively, according to different validated criteria. Advanced histological stages and non-adherence to treatment were associated with primary non-response to UDCA, while lower baseline alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels correlated with better responses to both UDCA and UDCA/fibrates. CONCLUSIONS: Clinical features of PBC in highly admixed Brazilians were similar to those reported in Caucasians and Asians, but with inferior rates of overlap syndrome with AIH. Response to UDCA was lower than expected and inversely associated with histological stage and baseline AST and ALP levels. Most of patients benefited from add-on fibrates, including ciprofibrate. A huge heterogeneity in response to UDCA therapy according to available international criteria was observed and reinforces the need of global standardization.

Evaluation of drug-induced liver injury as etiology for acute liver failure in Brazil.

INTRODUCTION AND OBJECTIVES: Little is known about the etiology of acute liver failure (ALF) in Latin America. The objective of this paper is to investigate the main etiologies of ALF in Brazil, including Drug Induced Liver Injury (DILI) using stringent causality criteria. PATIENTS OR MATERIAL AND METHODS: All the cases of individuals who underwent liver transplantation (LT) in 12 centers in Brazil for ALF were reviewed. When DILI was stated as the cause of ALF, causality criteria were applied on site by the main investigator in order to rule out other etiologies. RESULTS: 325 individuals had ALF mainly for unknown reasons (34%), DILI (27%) and AIH (18%). Reassessment of the 89 cases of DILI, using stringent causality criteria, revealed that in only 42 subjects could DILI be confirmed as the cause of ALF. Acetaminophen (APAP) toxicity (n = 3) or DILI due to herbal and dietary supplements (HDS) (n = 2) were not commonly observed. CONCLUSIONS: Undetermined etiology and DILI are the main causes of ALF in Brazil. However, APAP toxicity and DILI due to HDS are mostly uncommon.

Direct antiviral therapy for treatment of hepatitis C: A real-world study from Brazil.

INTRODUCTION AND OBJECTIVES: Direct antiviral agents (DAAs) including sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM) and ombitasvir, paritaprevir and dasabuvir were introduced 2015 in Brazil for treatment of hepatitis C virus (HCV) infection. The aims of this study were to assess effectiveness and safety of HCV treatment with DAA in real-life world in a highly admixed population from Brazil. MATERIALS AND METHODS: All Brazilian reference centers for HCV treatment were invited to take part in a web-based registry, prospectively conducted by the Brazilian Society of Hepatology, to assess outcomes of HCV treatment in Brazil with DAAs. Data to be collected included demographics, disease severity and comorbidities, genotype (GT), viral load, DAA regimens, treatment side effects and sustained virological response (SVR). RESULTS: 3939 patients (60% males, mean age 58±10 years) throughout the country were evaluated. Most had advanced fibrosis or cirrhosis, GT1 and were treated with SOF/DCV or SOF/SIM. Overall SVR rates were higher than 95%. Subjects with decompensated cirrhosis, GT2 and GT3 have lower SVR rates of 85%, 90% and 91%, respectively. Cirrhosis and decompensated cirrhosis in GT1 and male sex and decompensated cirrhosis in GT3 were significantly associated with no SVR. Adverse events (AD) and serious AD occurred in 18% and 5% of those subjects, respectively, but less than 1% of patients required treatment discontinuation. CONCLUSION: SOF-based DAA regimens are effective and safe in the heterogeneous highly admixed Brazilian population and could remain an option for HCV treatment at least in low-income countries.

The Portuguese Version of the Immunosuppressant Therapy Adherence Scale (ITAS) among Liver Transplant Recipient Patients: Translation and Psychometric Properties.

INTRODUCTION AND AIM: Transplant recipients are chronically ill patients who rely on medical treatment throughout life to achieve positive results. Despite that, medication nonadherence after liver transplantation is extremely common. The self-report, one of several methods for measuring adherence, is easy to apply and low cost. Thus, this study aims to translate and validate the Immunosuppressant Therapy Adherence Instrument (ITAS) in Brazilian Portuguese for liver transplant recipients. MATERIAL AND METHODS: A total of 139 liver transplant recipients were selected from a general hospital, who were assessed by using the Portuguese version of ITAS. The scale was translated based on the model proposed by Wild, et al. and its psychometric properties were assessed. RESULTS: The average Cronbach's α coefficient was 0.830. ITAS and Basel Assessment of Adherence with Immunosuppressive Medications Scale (BAASIS) presented significant correlation, with a Spearman's ρ coefficient = 0.300 (S = 309,580; p < 0.001). The area under the receiver operating characteristics (ROC) curve was 0.638 (95% CI: 0.557 - 0.715). Factor analysis results indicated that the carelessness factor model was the optimal model, and the factor "feeling worse" was the lowest. CONCLUSION: The Portuguese version of ITAS has adequate psychometric properties to measure adherence to immunosuppressant therapy.

New Onset Diabetes and Non-Alcoholic Fatty Liver Disease after Liver Transplantation.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is an emerging cause of graft dysfunction after liver transplantation (LT) frequently related to the development of new onset diabetes after LT (NODAT). This study was undertaken to evaluate the frequencies of NODAT and NAFLD after LT, to investigate their major risk factors and the impact of de novo or recurrent NAFLD in graft function. MATERIAL AND METHODS: 119 patients submitted to LT were prospectively evaluated. RESULTS: After 4 ± 1 years, NODAT, recurrent and de novo NAFLD were observed in 31%, 56% and 43% of the subjects, respectively. Only 3 patients had non-alcoholic steatohepatitis (NASH) without fibrosis. Other risk factors for NAFLD such as arterial hypertension (AHT), metabolic syndrome (MS), hypertriglyceridemia and obesity were seen in 51%, 50%, 35% and 24% of the subjects, respectively. In addition, insulin resistance (IR), assessed by HOMA-IR and ß-cell dysfunction, determined by HOMA-ß, were observed in 16% and 94% of the patients, respectively. Occurrence of NODAT was associated with male gender, higher waist circumference, higher HOMA-IR and lower HOMA-ß values. No correlation was found between NAFLD and NODAT, MS, hypertriglyceridemia, obesity and HOMAIR and HOMA-ß levels. CONCLUSIONS: NODAT, recurrent and de novo NAFLD are common after LT but are not associated with signs of graft dysfunction, possibly due to the low frequency of IR and NASH. No correlation is observed between NAFLD and NODAT, MS, hypertriglyceridemia, obesity and IR. ß-cell dysfunction and diabetes, however, are seen in most of the patients, possibly due to calcineurin inhibitor toxicity.

Hepatoportal sclerosis related to the use of herbals and nutritional supplements. Causality or coincidence?

 Introduction and aim. Non-cirrhotic idiopathic portal hypertension (NCIPH), also known as hepatoportal sclerosis (HPS) is a disease of uncertain etiology. However, various pathophysiological mechanisms has been postulated, including chronic or recurrent infections and exposure to drugs or toxins. In this context, it appears to be of multifactorial etiology or resulting from a portal vascular endothelium aggression. It is important to consider whether the use of dietary supplements and herbs can trigger or contribute to the occurance of HPS. We report a possible association of HPS with the consumption of herbals and / or dietary supplements. MATERIAL AND METHODS: We describe two cases of HPS in patients without known etiology causes associated with this disease. RESULTS: Both patients were females who were diagnosed with HPS following the consumption of Herbalife® products and putative anorexigenic agents in the form herbals infusions. Image-based analysis and the assessment of the histopathological alterations found in the livers confirmed the diagnosis. The histopatological analysis of liver samples from both patients showed portal tracts enlarged by fibrosis with disappearance or reduction in the diameter of the portal vein branches. In many portal tracts, portal veins branches were replaced by aberrant thin-walled fendiforme vessels. The bile ducts and branches of the hepatic artery show normal aspects. CONCLUSION: After the exclusion of other etiologic factors and a comprehensive analysis of clinical history, consumption of Herbalife® products and anorexigenic agents was pointed-out as a puttative predisposing factor for the development of the disease.

Impact of COVID-19 pandemic on surgical volume and outcomes in a terciary care center in Brazil.

BACKGROUNDS: COVID-19 pandemic led to a sharp decline in surgical volume worldwide due to the postponement of elective procedures. This study evaluated the impact of COVID-19 pandemic in surgical volumes and outcomes of abdominal surgery in high-risk patients requiring intensive care unit admission. METHODS: patients admitted for postoperative care were retrospectively evaluated. Data concerning perioperative variables and outcomes were compared in two different periods: January 2017-December 2019 and January 2020-December 2022, respectively, before (period I) and after (period II) the onset of COVID-19 pandemic. RESULTS: 1.402 patients (897 women, mean age 62+17 years) were investigated. Most of the patients underwent colorectal (n=393) and pancreato-biliary (n=240) surgery, 52% of elective procedures. Surgical volume was significantly lower in period II (n=514) when compared to period I (n= 888). No recovery was observed in the number of surgical procedures in 2022 (n=135) when compared to 2021(n=211) and 2020 (n=168). Subjects who underwent abdominal surgery in period II had higher Charlson comorbidity index (4,85+3,0 vs. 4,35+2,8, p=0,002), more emergent/urgent procedures (51% vs. 45%, p=0,03) and more clean-contaminated wounds (73,5% vs. 66,8%, p=0,02). A significant decrease in the volume of colorectal surgery was also observed (24% vs, 31%, p<0,0001) after the onset of COVID-19 pandemic, 125 (8,9%) died, no deaths due to COVID-19 infection. Mortality was higher in period II when compared to period I (11% vs. 8%, p=0,08). CONCLUSIONS: COVID-19 pandemic was associated with a decrease in surgical volume of high-risk patients without apparent recovery in recent years. No influence of COVID-19 was noted in postoperative mortality.

A new and simple score to predict adequate and deep response to ursodeoxycholic acid in patients with primary biliary cholangitis: the ALP-A score.

BACKGROUND: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cholangitis (PBC), but a significant proportion of patients do not respond adequately, leading to increased risk of adverse outcomes. This study aims to develop a new and straightforward predictive score to identify PBC patients likely to achieve a complete response to UDCA. METHODS: A logistic regression analysis was conducted using a derivation cohort of PBC patients to identify pre-treatment variables associated with response to UDCA. This analysis led to the development of the ALP-A score, calculated as: Age at diagnosis divided by (alkaline phosphatase at diagnosis/upper limit of normal). ALP-A score accuracy was evaluated using the area under the ROC curve, validated with a large external cohort from Brazil. Additionally, the correlation between the ALP-A score and the previously validated UDCA response score (URS) was assessed. RESULTS: ALP-A score had good predictive power for adequate (AUC 0.794; 95% CI, 0.737-0.852) and deep (0.76; 95% CI, 0.69-0.83) UDCA response at 1 year of treatment. A cutoff score of 17 and 23 points was determined to be the optimal threshold for distinguishing adequate and deep responders, respectively, from non-responders. ALP-A score demonstrated a sensitivity of 73%, specificity of 71%, positive predictive value of 65%, negative predictive value of 78%, and overall accuracy of 72% for biochemical response. The URS displayed similar discriminative ability (AUC 0.798; 95% CI, 0.741-0.855). CONCLUSION: ALP-A score performs comparably to URS but offers the great advantage of simplicity for routine clinical use. It serves as a valuable tool to identify PBC patients less likely to respond to UDCA treatment, facilitating early consideration of alternative therapeutic approaches.

Public knowledge and attitudes toward liver diseases and liver cancer in the Brazilian population: a cross sectional study.

Background: Little is known about the knowledge of the Brazilian population regarding prevention/screening/diagnosis of cirrhosis and hepatocellular carcinoma (HCC). We aimed to investigate the public knowledge/attitudes toward liver diseases in Brazil. Methods: A cross-sectional survey was conducted in which 1.995 adults were prospectively interviewed regarding knowledge about cirrhosis/HCC and attitudes toward vaccination and viral hepatitis (VH) testing. Findings: Most of the Brazilian subjects believe that alcohol abuse (63%-87%), NAFLD (29%-53%) and smoking (31%-47%) are the leading causes of cirrhosis/HCC. VH were less often linked to both diseases. Brazilians agreed that NAFLD is a risk factor for cirrhosis, cancer and cardiovascular diseases; 66%, 48% and 40% were submitted to hepatitis B vaccination and hepatitis B and C testing, particularly those with older age, higher level of education and income. Interpretation: VH was not considered by the majority of the Brazilians as an important cause liver disease, leading a large proportion of those subjects to neglect hepatitis B vaccination and hepatitis B and C testing. Funding: This work was supported by Brazilian Liver Institute.

Impact of baseline abnormal liver enzymes in the outcome of COVID-19 infection.

Background: Little is known about the significance of liver function tests (LFT) abnormalities in COVID-19 and their impact on disease outcomes. The aims of the study were to evaluate abnormalities of LFT in patients with COVID-19 and their impact on disease severity, mortality, and correlation with leukocyte markers of inflammation. Methods: All patients with COVID-19 admitted to the emergency department (ED) of a single reference center were retrospectively evaluated. Data were collected using an electronic medical database covering the following variables: demographics, baseline complete blood count (CBC) and ratios, neutrophil-lymphocyte (NLR) and monocyte-lymphocyte ratios (MLR), systemic immune-inflammation index (SII), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Disease severity was defined by the presence of organ failure (OF) or requirement for intensive care unit (ICU) support. Mortality was considered as patient death during hospitalization. Results: A total of 1,539 subjects (799 women, mean age 57±18 years) with COVID-19 were evaluated. Abnormal AST and/or ALT were seen in 50% of them, with a frequency and magnitude that significantly correlated with leukocyte count and ratios. Both LFT were significantly associated with requirement for hospital and ICU admission and mortality. High AST levels were significantly associated with the presence, number, and types of OFs and in-hospital length of stay (LOS). Elevated ALT was also significantly associated with the aforementioned variables, with the exception of OFs presence, circulatory failure and LOS. Conclusions: LFT abnormalities are frequently seen in COVID-19 patients, reflect SARS-CoV-2 associated inflammation and may predict adverse outcomes. LFT may be useful to aid decision-making in the ED for hospital admission or scheduled outpatient reevaluation.

Impact of tacrolimus intra-patient variability in adverse outcomes after organ transplantation.

Tacrolimus (Tac) is currently the most common calcineurin-inhibitor employed in solid organ transplantation. High intra-patient variability (IPV) of Tac (Tac IPV) has been associated with an increased risk of immune-mediated rejection and poor outcomes after kidney transplantation. Few data are available concerning the impact of high Tac IPV in non-kidney transplants. However, even in kidney transplantation, there is still a controversy whether high Tac IPV is indeed detrimental in respect to graft and/or patient survival. This may be due to different methods employed to evaluate IPV and distinct time frames adopted to assess graft and patient survival in those reports published up to now in the literature. Little is also known about the influence of high Tac IPV in the development of other untoward adverse events, update of the current knowledge regarding the impact of Tac IPV in different outcomes following kidney, liver, heart, lung, and pancreas tran splantation to better evaluate its use in clinical practice.