Diagnosis and staging of fibrosis in patients with chronic hepatitis C: comparison and critical overview of current strategies

Leandro César Mendes, Raquel SB Stucchi, Aline G Vigani Department of Infectious Diseases, State University of Campinas, Campinas, SP, Brazil Abstract: In the past years, what has always been considered undisputed true in liver fibrosis staging has been challenged. Diagnostic performance of histological evaluation has proven to be significantly influenced by sample- and observer-related variabilities. Differentiation between lower levels of fibrosis remains difficult for many, if not all, test modalities, including liver biopsy but, perhaps, such a distinction is not indispensable in light of current therapeutic approaches. Biomarkers and elastography offer, nonetheless, high predictive values for advanced fibrosis and cirrhosis and correlate well with liver-related outcomes. Necroinflammation, steatosis, and hemodynamic changes may significantly interfere with elastography-based techniques, and longitudinal follow-up strategies must be tailored in light of these findings. Knowledge of different test modalities and diagnostic performance indicators can allow for better clinical decision-making and resource allocation. Keywords: chronic hepatitis C, fibrosis, staging, elastography, biomarker

Perfusion Fluid Contamination in Relation to Recipient Survival and Acute Cellular Rejection in Orthotopic Liver Transplantation: Retrospective Analysis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Introduction. A perfusion fluid used in the preservation of a grafted liver represents a medium suitable for microorganism growth. This study investigated the prevalence of perfusion fluid contamination, acute cellular rejection (ACR) episodes, and patient survival rate. Method. This is a retrospective study, based on an electronic database allocating cases of orthotopic liver transplantation. The exclusion criteria were as follows: having been submitted to multiple organ transplantation, liver retransplantation only, and those whose samples had not been collected or sent on the back table procedure or were unobtainable (usually the samples were sent when there was donor infection suspicion/positivity). Our posttransplantation infection prophylactic protocol consisted of ampicillin/sulbactam for 72 hours. The variables in the study were as follows: fluid contamination, presence of acute cellular rejection (ACR, Banff classification), and recipient survival at the first year. Statistical analysis was performed using descriptive statistics and chi-square with Fisher exact test considering significant P < .05. Results. We observed perfusion fluid contamination in 15/121 (12.39%). The agents were as follows: Klebsiella pneumoniae in 6 (4.96%), Staphylococcus epidermidis in 5 (4.13%), and Acinetobacter baumanii in 3 (2.48%) and negative cultures in 106 (87.60%). Only 1 patient had matching for donor infection and positivity hemoculture after the transplantation (K pneumoniae) and he was the only patient associated with fluid infection and death. The recipients who had their fluid preservation with positive cultures had more ACR and the survival rate was similar among those with or without infection. Conclusion. Optimization of microbiological procedures can be performed including fungal and bacterial cultures.43413131315Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Serological Profile of Pretransplantation Liver Patients

Introduction. A liver transplantation is the first choice of treatment for patients with hepatic insufficiency due to chronic diseases. Infections in the postoperative period represent one of the main causes of mortality in these cases. However, few articles have evaluated the predominance of certain infectious diseases and their influence on postoperative mortality. Methods. We retrospectively evaluated the medical records of 236 patients who underwent liver transplantation from January 1997 to January 2007. In these records we checked the serological profiles for these diseases: toxoplasmosis, syphilis, human T lymphotropic virus (HTLV) I and II infection, Chagas disease, hepatitis A, hepatitis B, hepatitis C, paracoccidioidomycosis, tuberculosis, acquired immunodeficiency syndrome, cytomegalovirus (CMV), and mononucleosis (Epstein-Barr virus [EBV]). The statistical analysis was performed by table frequencies. Results. CMV showed positivity (CMV-IgG) in 94.7% of patients, 95.8% for EBV, 33.3% for toxoplasmosis, 47.9% for hepatitis C, and 5% for hepatitis B. Conclusion. Our analysis showed the importance of serological investigations and diagnostic examinations before the transplantation procedure, seeking to minimize possible reactivation of the disease after the use of immunosuppression drugs, particularly in the first 6 months after transplantation, or even to avoid a primary infection.42249149

Cytomegalovirus, Human Herpesvirus-6, and Human Herpesvirus-7 in Adult Liver Transplant Recipients: Diagnosis Based on Antigenemia

Human herpesvirus (HHV)-6, HHV-7, and cytomegalovirus (CMV) that remain latent after primary infection can be reactivated during immunosuppression following organ transplantation in liver transplant recipients. The aim of this study was to monitor active infections for HHV-6, HHV-7, and CMV among adult liver transplantation recipients using antigenemia detected by an immunoperoxidase staining. Twenty-eight adult liver transplant patients were monitored using antigenemia in blood samples obtained at the time of transplantation, as well as weekly in the first month and once a month for 6 months. Of these patients, 28.5% showed positive CMV antigenemia; 39.2%, HHV-6 antigenemia; and 14.2%, HHV-7 antigenemia. The detection of the three viruses was considered to be independent of one another (P > .05). The results described above showed that few patients remain free of beta herpesviruses after liver transplantation. Most patients were infected sequentially and not concurrently. Antigenemia has been considered useful to detect active HHV-6 and HHV-7 infections. Antigenemia can be more efficiently interpreted when compared with polymerase chain reaction results, although other studies are necessary to establish the reference of HHV-6 and HHV-7 antigenemia.4341357135

Survival analysis of obese patients undergoing liver transplantation

Introduction. The influence of preoperative obesity in liver transplanted patients remains undetermined. Objective. To analyze the survival of obese patients undergoing liver transplantation. Methods. We calculated the body mass index (BMI; kg/m(2)) of 244 liver transplantation patients. All transplantations were performed from September 1991 to December 2006. The patients were divided according to the BMI values: nonobese (NO) patients (BMI 30). Pre- and postoperative data were used. The following statistical tests were employed: Student's t test, Kaplan-Meier survival, and Cox-Mantel tests. Results. Group O was composed of 38 individuals (15.3%) with BMI of 33.1, and the BMI of NO was 24. Group O showed an average age of 50.1 years and group NO, 45.5 years (P .05). A Cox proportional hazard analysis showed that the survival time in this study was related to red blood cell transfusions, recipient sodium, MELD score, donor sodium, and age. Recipient age was a main factor in multiple regression analysis for obese patients in this study. Conclusion. There was no significant difference between O and NO for the 1-year and long-term survivals, but older patients displayed lower survival times.39103225322

Anxiety Levels Observed in Candidates for Liver Transplantation

Introduction. Anxiety can be considered an emotional state that does not present itself at the same intensity in all patients, and can be classified into 3 levels: mild, moderate, and severe. The patient, upon entering the waiting list for transplantation, reflects on the decision taken, which leaves him constantly anxious about the idea of possible death. Objective. This study had the aim of evaluating the degree of anxiety observed in orthotopic liver transplantation (OLT) candidates and whether there was a correlation between anxiety and etiologic diagnosis. Methods. This study was a prospective study where the patients underwent psychological evaluation by Beck Anxiety Inventory (BAT). The anxiety level was minimal, mild, moderate, or severe. The Model for End-Stage Liver Disease (MELD) score and etiology were recorded. Results. The level of anxiety found were as follows: 55% minimal, 27% mild, 12% moderate, and 7% severe. The correlation between level of anxiety and etiologic diagnosis showed that 71% of patients with alcoholic cirrhosis and 60% of those with liver cancer showed a minimal degree of anxiety and 27% of patients with autoimmune cirrhosis had severe anxiety. Conclusion. We found that in patients with autoimmune hepatitis, the degree of anxiety was more pronounced. It is believed that the absence of physical symptoms is an important factor when observing anxiety in OLT candidates.42251351

Prognostic Factors for Hepatocellular Carcinoma Recurrence: Experience With 83 Liver Transplantation Patients

Introduction. Orthotopic liver transplantation (OLT) is a rational therapeutic option for early-stage hepatocellular carcinoma (HCC) providing a potential cure and improving survival. Methods. This retrospective study of a longitudinal cohort used an electronic database collected prospectively from September 1997 to May 2010. The variables were gender, age (years), and alpha-fetoprotein (AFP) level (ng/mL). In explanted livers we observed: microvascular or macrovascular invasion, number of nodules and their largest size, Edmondson-Steiner histological differentiation, incidental tumor transarterial chemoembolization (TACE), Milan criteria, and previous down-staging. Results. Five of 83 (6.0%) subjects including 68 (82%) males with a mean time to diagnosis of 9 months experienced tumor relapses. Mean patient age at HCC recurrence was 55.3 years for male and 44.6 years for female subjects. Vascular invasion was detected in 17/83 (20.5%) subjects, namely 2% of macrovascular invasion, and 52.5% with expanded Milan criteria due to an increased number and size of nodules in the explanted livers. An incidental tumor was observed in 29.5% of cases. Preoperative TACE treatment was performed in 13 (15.6%) patients. None of the patients who had a HCC recurrence had undergone TACE. APP level at the time of recurrence was around 1,900 ng/mL. The predictive factor for mortality was nodule size (P = .04; hazard ratio = 0.0269; confidence interval [CI], 95% 0.0094-0.299). Conclusion. Patients with relapses showed the worst survival and tumor size was a predictive factor for recurrence.4341362136

Monitoring and Detection of Cytomegalovirus in Liver Transplant Recipients

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Cytomegalovirus (CMV) is a p-herpesvirus. CMV infections are a common complication contributing to morbidity and mortality after liver transplantation. Among organ transplant recipients, CMV can reactivate from latency during the first 6 months. This prospective study performed from February 2008 to December 2009 examined liver transplant recipients during the first 6 months. Two methods were performed to detect CMV infections: antigenemia (AGM) and nested (PCR). Ninety-four patients, including 72 men (76.6%) and 22 women (23.4%) underwent liver transplantation during this period. We analyzed 575 samples including 465 for AGM and PCR. Forty-three (9.25%) showed positive AGM as detected 2 to 179 days posttransplantation with a mean of 50 days and a median of 35 days, and 93/465 (20%) showed positive PCR at 0 to 186 days posttransplantation with a mean of 31 days and a median of 38 days. Among the 43 antigenemia patients, 38 samples were positive for up to 5 cells 18 of which were PCR-positive. Five samples were positive with more than 5 cells, including 3 that were PCR-positive. Only 4.51% had AGM and were PCR-positive in the same sample. Despite only 9.25% (43/465) showing AGM, the current study suggested the utility of routine monitoring to detect early CMV infection among liver transplantation patients seeking to reduce morbidity and mortality.43413601361Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Clearance of persistent SARS-CoV-2 RNA detection in a NF kappa B-Deficient patient in association with the ingestion of human breast milk: a case report

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patient