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Post-transplant lymphoproliferative disorder (PTLD) is a major and potentially life-threatening complication after solid-organ transplantation. The aim of this study was to describe the disease characteristics, clinical practices, and survival related to PTLD in adult orthotopic liver transplant (OLT) recipients in South America. We conducted a survey at four different transplant groups from Argentina, Brazil, and Chile. Among 1621 OLT recipients, 27 developed PTLD (1.7%); the mean age at diagnosis was 53.7 (± 14) yr with a mean time of 39.7 (± 35.2) months from OLT to PTLD diagnosis. Initial therapy included reduction in immunosuppression alone in 23.1% of the patients. Either rituximab or chemotherapy was employed as initial or second-line therapy in 76.9% of the patients. PTLD location was frequently extranodal (80.7%) and mostly involving the transplanted liver (59.3%). The overall survival at one and five yr post-PTLD diagnosis was 53.8% and 46.2%, respectively. Significant univariate risk factors for post-PTLD mortality included lactate dehydrogenase ≥ 250 U/L (HR 9.66, p = 0.02), stage III/IV PTLD (HR 5.34, p = 0.004), and HCV infection (HR 7.68, p = 0.01). In conclusion, PTLD in OLT adult recipients is predominantly extranodal, and although mortality is high, long-term survival is possible., (© 2013 John Wiley & Sons A/S.)

Introduction and Objectives: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. Patients: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. Results: Overall, 4.6% (CI 3.7-5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14-25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P < .0001). Cirrhosis was independently associated with death [OR 3.1 (CI 1.9-4.8); P < .0001], adjusted by age, gender, and body mass index >30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). Conclusions: SARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIFC had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380. [ABSTRACT FROM AUTHOR]

Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) is an uncommon cause of liver disease presenting with a wide range of phenotypes and disease severity, acute hepatitis mimicking viral hepatitis to autoimmune hepatitis, steatosis, fibrosis or rare chronic vascular syndromes. Disease severity ranges from asymptomatic liver test abnormalities to acute liver failure. DILI has been traditionally classified in predictable or intrinsic (dose-related) or unpredictable (not dose-related) mechanisms. Few prospective studies are assessing the real prevalence and incidence of hepatotoxicity in the general population. DILI registries represent useful networks used for the study of liver toxicity, aimed at improving the understanding of causes, phenotypes, natural history, and standardized definitions of hepatotoxicity. Although most of the registries do not carry out population-based studies, they may provide important data related to the prevalence of DILI, and also may be useful to compare features from different countries. With the support of the Spanish Registry of Hepatotoxicity, our Latin American Registry (LATINDILI) was created in 2011, and more than 350 DILI patients have been recruited to date. This position paper describes the more frequent drugs and herbsinduced DILI in Latin America, mainly focusing on several features of responsible medicaments. Also, we highlighted the most critical points on the management of hepatotoxicity in general and those based on findings from our Latin American experience in particular. [ABSTRACT FROM AUTHOR]

Nimesulide is a non-steroidal anti-inflammatory drug still marketed in many countries. We aim to analyze the clinical phenotype, outcome, and histological features of nimesulide-induced liver injury (nimesulide-DILI). We analyzed 57 cases recruited from the Spanish and Latin American DILI registries. Causality was assessed by the RUCAM scale. Mean age of the whole case series was 59 years (86% women) with a median time to onset of 40 days. A total of 46 patients (81%) were jaundiced. Nimesulide-DILI pattern was hepatocellular in 38 (67%), mixed in 12 (21%), and cholestatic in 7 (12%) cases. Transaminases were elevated with a mean of nearly 20-fold the upper limit of normality (ULN), while alkaline phosphatase showed a twofold mean elevation above ULN. Total bilirubin showed a mean elevation of 13-fold the ULN. Liver histology was obtained in 14 cases (25%), most of them with a hepatocellular pattern. Median time to recovery was 60 days. Overall, 12 patients (21%) developed acute liver failure (ALF), five (8.8%) died, three underwent liver transplantation (5.3%), and the remaining four resolved. Latency was ≤ 15 days in 12 patients (21%) and one patient developed ALF within 7 days from treatment initiation. Increased total bilirubin and aspartate transaminase levels were independently associated with the development of ALF. In summary, nimesulide-DILI affects mainly women and presents typically with a hepatocellular pattern. It is associated with ALF and death in a high proportion of patients. Shorter (≤ 15 days) duration of therapy does not prevent serious nimesulide hepatotoxicity, making its risk/benefit ratio clearly unfavorable. [ABSTRACT FROM AUTHOR]

Introduction: Although the effectiveness of direct‐acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) has been reported in real‐world settings, predictive factors of treatment failure are lacking. Therefore, we sought to explore the baseline predictors of treatment response to DAAs. Methods: This was a prospective multicenter cohort study from the Latin American Liver Research Educational and Awareness Network (LALREAN) including patients who received DAA treatment from May 2016 to April 2019. A multivariate logistic regression model was conducted to identify variables associated with unachieved sustained virological response (SVR), defined as treatment failure (odds ratios [OR] and 95% confidence intervals [CIs]). Results: From 2167 patients (55.2% with cirrhosis) who initiated DAA therapy, 89.4% completed a full‐course treatment (n = 1938). Median treatment duration was 12 weeks, and 50% received ribavirin. Definitive suspension due to intolerance or other causes was observed in only 1.0% cases (n = 20). Overall non‐SVR12 was 4.5% (95% CI, 3.5‐5.7). There were no significant differences in treatment failure according to HCV genotypes and the degree of fibrosis. Independently associated variables with DAA failure were liver function impairment according to the Child‐Pugh score B OR, 2.09 (P =.06), Child‐Pugh C OR, 11.7 (P <.0001); and liver transplant (LT) recipient OR, 3.75 (P =.01). Conclusion: In this real‐life setting, higher DAA treatment failure rates were observed in patients with decompensated cirrhosis and in LT recipients. These predictive baseline factors should be addressed to individualize the appropriate time‐point of DAA treatment (NCT03775798; www.clinicaltrials.gov). Highlights: SVR12 failure in clinical practice is low in Latin America (4.5%). End stage liver disease (Child B/C scores) and liver transplantation were independent predictors of DAA failure. Early DAA treatment to prevent disease progression is needed to avoid nonresponse to treatment. [ABSTRACT FROM AUTHOR]

Introduction and aim: Liver transplantation (LT) for acute liver failure (ALF) still has a high early mortality. We aimed to evaluate changes occurring in recent years and identify risk factors for poor outcomes. Material and methods: Data were retrospectively obtained from the Argentinean Transplant Registry from two time periods (1998-2005 and 2006-2016). We used survival analysis to evaluate risk of death. Results: A total of 561 patients were listed for LT (69% female, mean age 39.5 ± 16.4 years). Between early and later periods there was a reduction in wait-list mortality from 27% to 19% (p < 0.02) and 1-month post-LT survival rates improved from 70% to 82% (p < 0.01). Overall, 61% of the patients underwent LT and 22% died on the waiting list. Among those undergoing LT, Cox regression analysis identified prolonged cold ischemia time (HR 1.18 [1.02-1.36] and serum creatinine (HR 1.31 [1.01-1.71]) as independent risk factors of death post-LT. Etiologies of ALF were only available in the later period (N = 363) with indeterminate and autoimmune hepatitis accounting for 28% and 26% of the cases, respectively. After adjusting for age, gender, private/public hospital, INR, creatinine and bilirubin, and considering LT as the competing event, indeterminate etiology was significantly associated with death (SHR 1.63 [1.06-2.51] and autoimmune hepatitis presented a trend to improved survival (SHR 0.61 [0.36-1.05]). Conclusions: Survival of patients with ALF on the waiting list and after LT has significantly improved in recent years. Indeterminate cause and autoimmune hepatitis were the most frequent etiologies of ALF in Argentina and were associated with mortality. [ABSTRACT FROM AUTHOR]

• Host and viral genetic variability determines the outcome of acute hepatitis B in subgenotype F1b. • Patients with worse clinical outcome exhibit positive selection sites on HLA epitopes. • Mutations in the HBV precore/core region are higher in patients with worse clinical outcome. • Heterogeneous and complex HBV quasispecies relate to worse outcome of acute infection. To assess the association of viral and host genetic variability with the outcome of acute infection with hepatitis B virus subgenotype F1b (HBV/F1b). The cohort consisted of 26 patients with acute HBV/F1b infection who exhibit different outcomes: spontaneous resolution (n = 10), progression to chronic hepatitis (n = 10) and acute liver failure (n = 6). HLA SNPs (rs3077, rs9277542, rs2856718 and rs7453920) were determined. The S gene and core promoter/precore/core region were direct sequenced, and this latter region was also ultra-deep sequenced. Mean number of mutations, mutation rate, Shannon entropy, positive selection sites and mutational patterns of quasispecies were compared between groups. HLA SNPs were associated with spontaneous resolution or progression to chronic hepatitis, but not with the development of acute liver failure. The mean number of mutations in the S gene was similar among the three groups. Patients with spontaneous resolution had the lowest number of mutations, mutation rates and Shannon entropy values in the precore/core compared to the other two groups. Ten positive selection sites mapped on HLA-restricted epitopes were related to progression to chronic hepatitis and acute liver failure. Mutations T1753C, A1762T, G1764A, C1766T, T1768A G1896A, G2092T and T2107C were associated with acute liver failure and progression to chronic hepatitis. Highly heterogeneous and complex HBV precore/core carrying specific point mutations, combined with the host HLA background, were associated with a worse clinical outcome of acute HBV/F1b infection. [ABSTRACT FROM AUTHOR]