Portopulmonary Hypertension

Portopulmonary hypertension (PPH) is characterized by the development of pulmonary arterial hypertension (PAH) associated with portal hypertension, with or without liver disease. It is defined as a mean pulmonary artery pressure (MPAP) greater than 25 mmHg, pulmonary vascular resistance (PVR) above 240 dynes.s.cm-5, pulmonary artery occlusion pressure (PAOP) normal when less than 15 mmHg or transpulmonary gradient (TPG) > 10 mmHg. In the pulmonary hypertension classification PPH is classified in Group I. Pulmonary arterial hypertension in association with cirrhosis and portal hypertension is underdiagnosed. Epidemiological studies estimated that about 2–6% of patients with portal hypertension develop PPH. Mortality is directly proportional to measured MPAP and PVR. Mean pulmonary artery pressure is an independent predictor of mortality, and many centers consider that values greater than 50 mmHg is an absolute contraindication to liver transplantation (LT). The aim of the review is to explore the current aspects of PPH relative to concept, diagnosis, and treatment

Gender Differences in COVID-19 Among Liver Transplant Recipients: Results from a Multicenter Brazilian Cohort

Introduction: Existing literature presents varying perspectives on the impact of COVID-19 on liver transplant recipients.However, no research has specifically investigated the role of gender differences in the manifestation of COVID-19 among liver transplant recipients. This study aims to examine the effects of COVID-19 on liver transplant recipients, with a focus on gender differences in disease presentation and progression. Methods: Conducted as a multicenter historical cohort study, this research collected patient records through an online questionnaire. Assessing COVID-related mortality was the main objective. Additionally, demographic, clinical, and laboratory data pertaining to disease presentation and progression werecollected. Results: The study included a total of 283 patients, of whom 76 were female and 206 were male. The median follow-up period for males was 99 days (IQR 38-283), while for females, it was 126 days (IQR 44-291). A higher prevalence of cardiovascular disease was observed in males (p=0.002). Females frequently experienced a loss of smell (p=0.021), whereas males commonly exhibited fever (p=0.031). Levels of ALT and gamma-glutamyl transferase were significantly elevated in males (p=0.008 and 0.004, respectively). Although there was a trend towards increased mortality in males, it did not reach statistical significance. Conclusion: This study is the first attempt to investigate gender differences in COVID-19 among liver transplant recipients. Our findings highlight the need for a comprehensive and personalised approach to treating this patient population and underscore the importance of further elucidating the disease presentation in these individuals

Impact of Brazilian expanded criteria for liver transplantation in patients with hepatocellular carcinoma: a multicenter study

Introduction and objectives: Hepatocellular carcinoma (HCC) is one of the main indications for orthotopic liver transplantation (OLT). In Brazil, selection criteria for HCC is an expanded version of the Milan Criteria (MC), the so-called ''Brazilian Milan Criteria'' (BMC). Our aims were to evaluate post-OLT outcomes in patients with HCC and analyze the BMC performance. Materials and Methods: We conducted a multicenter, retrospective cohort study, analyzing medical records of 1,059 liver transplant recipients with HCC. Tumor was staged according to MC and BMC and correlated with overall survival (OS) and disease-free survival (DFS). We compared the ability of MC and BMC to predict OS and DFS using Delta C-statistic. Results: Post-OLT OS were 63% in five years and HCC recurrence was observed in 8% of patients. At diagnosis, 85% of patients were within MC. Patients within MC at diagnosis and in the explant showed a higher OS and DFS than patients outside MC and within BMC and patients outside both criteria (p < 0.001). Patients outside MC in the explant had an increased risk of tumor recurrence (HR: 3.78; p < 0.001) and poor survival (HR:1.77; p = 0.003). The BMC presented a lower performance than MC in properly classifying patients regarding recurrence risk. Conclusions: In a large Brazilian cohort of HCC patients submitted to liver transplantation, we observed satisfactory overall survival and recurrence rates. However, patients transplanted within the Brazilian expanded criteria had lower OS and DFS when compared to patients within MC, which may generate future discussions regarding the criteria currently used

R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation

Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging +/- alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management.Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085).Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of -4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3-6 cm: SHR = 1.83,1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101-1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber's c-index was 0.76 (95% CI 0.72-0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72-0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1-2 points; 15.1%), high (3-6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber's c-index of 0.78; 95% CI 0.73-0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria.Clinical Trials Registration: NCT03775863.Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables inde-pendently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL)

Detection of human herpesvirus-7 by qualitative nested-PCR: comparison between healthy individuals and liver transplant recipients Detecção de herpesvirus humano-7 por nested-PCR qualitativo: comparação entre indivíduos sadios e receptores de transplante hepático

Diagnosis of human herpesvirus-7 active infection in transplant patients has proved difficult, because this virus is ubiquitous and can cause persistent infections in the host. The significance of viral DNA detected in leukocytes by PCR is unclear and cross-reaction in serological tests may occur. This study aimed to evaluate nested-PCR to detect human herpesvirus-7 active infection in liver transplant recipients compared to healthy individuals. human herpesvirus-7 nested-PCR was performed on leukocytes and sera of 53 healthy volunteers and sera of 29 liver transplant recipients. In healthy volunteers, human herpesvirus-7 was detected in 28.3% of leukocytes and 0% of serum. human herpesvirus-7 was detected in sera of 48.2% of the liver transplant recipients. Nested-PCR on DNA extracted from leukocytes detected latent infection and the study suggests that nested-PCR performed on serum could be useful to detect human herpesvirus-7 active infection in liver transplant recipients.<br>Diagnóstico da infecção ativa pelo herpesvirus humano-7 é difícil devido ao fato deste vírus ser ubíquo e poder causar infecção persistente no hospedeiro. O significado da detecção do DNA viral por reação em cadeia da polimerase não é claro e, reações cruzadas podem ocorrer em testes sorológicos. O objetivo deste estudo foi avaliar a nested-PCR para detectar infecção ativa pelo herpesvirus-7 em receptores hepáticos comparando com indivíduos sadios. Nested-PCR para herpesvirus-7 foi realizado em leucócitos e soro de 53 voluntários sadios e em soro de 29 receptores hepáticos. Nos voluntários sadios, herpesvirus-7 foi detectado em 28,3% de leucócitos e 0% de soro. herpesvirus-7 foi detectado em soro de 48,2% de receptores hepáticos. Nested-PCR em DNA extraído de leucócitos detectou infecção latente e o estudo sugere que nested-PCR realizada em soro poderia ser útil para detectar infecção ativa por herpesvirus-7 em receptores de fígado

Aplicação do escore MELD em pacientes submetidos a transplante de fígado: análise retrospectiva da sobrevida e dos fatores preditivos a curto e longo prazo The application of MELD score in patients submitted to liver transplantation: a retrospective analysis of survival and the predictive factors in the short and long term

RACIONAL: Utiliza-se o escore MELD (Model End-Stage Liver Disease) para o prognóstico da mortalidade em lista de espera para transplante de fígado e, em alguns estudos, para predição da sobrevida pós-operatória a longo prazo. OBJETIVO: Verificar a aplicação do escore MELD como predição da sobrevida após o transplante. MÉTODOS: Por intermédio de dados coletados prospectivamente efetuou-se um estudo de coorte longitudinal retrospectivo em 232 pacientes. Excluíram-se os retransplantes, insuficiência hepática aguda, crianças e enxertos duplos ou reduzidos. Avaliaram-se os dados dos doadores: idade, sexo, peso, creatinina, bilirrubina, sódio, aspartato aminotransferase, antecedentes pessoais, causa da morte, presença de esteatose, número de critérios expandidos do doador e índice de risco do doador. Em relação aos receptores, analisaram-se as variáveis: sexo, idade, peso, doença hepática, pontos de Child-Turcotte-Pugh, escore MELD, depuração de creatinina, sódio, tempos de isquemia e de hospitalização, quantidade de hemoderivados transfundidos, presença e grau de disfunção do enxerto. A análise estatística foi efetuada usando-se a análise de regressão univariada e/ou múltipla, estatística 'c', teste exato de Fisher, método de Kaplan-Meier (teste log-rank) para sobrevida, e análise de regressão de Cox para risco de óbito ajustado para as condições clínicas. RESULTADOS: O ponto de corte MELD para sobrevida foi 20 e de Child-Turcotte-Pugh foi 11,5. Para escore MELD maior ou igual a 20, os fatores preditivos de sobrevida foram: volume de sangue transfundido, disfunção do enxerto e o sódio do doador. Para os hiponatrêmicos os fatores preditivos de sobrevida foram: volume de sangue transfundido, disfunção do enxerto e sódio do doador. A sobrevida estimada para pacientes com escore MELD >25 foi menor ao final de 12 meses (68,86% vs 39,13%). A sobrevida estimada para os pacientes sem hiponatremia foi maior (65,16% vs 44,44%). A sobrevida aos 5 e 10 anos também seguiu o mesmo padrão. O uso de doadores limítrofes não alterou a sobrevida, mas quando se utilizou o índice de risco do doador observou-se que a sobrevida foi maior para pacientes com índice de risco do doador menor que 1,7 (63,62% vs 53,70%). A associação deste índice com o escore MELD não mostrou diferença estatística em relação à sobrevida. Observou-se que a falência e disfunção do enxerto foram associadas ao número crescente de critérios expandidos do doador. Os receptores de doadores maiores de 50 anos tiveram menor sobrevida (65,58% vs 38,40%) e o escore delta-MELD não discriminou a sobrevida. CONCLUSÃO: A sobrevida dos receptores a curto e longo prazo é associada a escores MELD acima de 25, ao volume de sangue transfundido, à disfunção do enxerto, à hiponatremia, à idade do doador acima de 50 anos e àqueles doadores com índice de risco do doador acima de 1,7.<br>BACKGROUND: The model for end-stage liver disease (MELD) was developed to predict short-term mortality in patients with cirrhosis. There are few reports studying the correlation between MELD and long-term posttransplantation survival. AIM: To assess the value of pretransplant MELD in the prediction of posttransplant survival. METHODS: The adult patients (age >18 years) who underwent liver transplantation were examined in a retrospective longitudinal cohort of patients, through the prospective data base. We excluded acute liver failure, retransplantation and reduced or split-livers. The liver donors were evaluated according to: age, sex, weight, creatinine, bilirubin, sodium, aspartate aminotransferase, personal antecedents, brain death cause, steatosis, expanded criteria donor number and index donor risk. The recipients' data were: sex, age, weight, chronic hepatic disease, Child-Turcotte-Pugh points, pretransplant and initial MELD score, pretransplant creatinine clearance, sodium, cold and warm ischemia times, hospital length of stay, blood requirements, and alanine aminotransferase (ALT >1,000 UI/L = liver dysfunction). The Kaplan-Meier method with the log-rank test was used for the univariable analyses of posttransplant patient survival. For the multivariable analyses the Cox proportional hazard regression method with the stepwise procedure was used with stratifying sodium and MELD as variables. ROC curve was used to define area under the curve for MELD and Child-Turcotte-Pugh. RESULTS: A total of 232 patients with 10 years follow up were available. The MELD cutoff was 20 and Child-Turcotte-Pugh cutoff was 11.5. For MELD score > 20, the risk factors for death were: red cell requirements, liver dysfunction and donor's sodium. For the patients with hyponatremia the risk factors were: negative delta-MELD score, red cell requirements, liver dysfunction and donor's sodium. The regression univariated analyses came up with the following risk factors for death: score MELD > 25, blood requirements, recipient creatinine clearance pretransplant and age donor >50. After stepwise analyses, only red cell requirement was predictive. Patients with MELD score < 25 had a 68.86%, 50,44% and 41,50% chance for 1, 5 and 10-year survival and > 25 were 39.13%, 29.81% and 22.36% respectively. Patients without hyponatremia were 65.16%, 50.28% and 41,98% and with hyponatremia 44.44%, 34.28% and 28.57% respectively. Patients with IDR > 1.7 showed 53.7%, 27.71% and 13.85% and index donor risk <1.7 was 63.62%, 51.4% and 44.08%, respectively. Age donor > 50 years showed 38.4%, 26.21% and 13.1% and age donor <50 years showed 65.58%, 26.21% and 13.1%. Association with delta-MELD score did not show any significant difference. Expanded criteria donors were associated with primary non-function and severe liver dysfunction. Predictive factors for death were blood requirements, hyponatremia, liver dysfunction and donor's sodium. CONCLUSION: In conclusion MELD over 25, recipient's hyponatremia, blood requirements, donor's sodium were associated with poor survival