Bone marrow mesenchymal stem cells in acute-on-chronic liver failure grades 2 and 3 : a phase I-II randomized clinical trial

Introduction: Acute-on-chronic liver failure (ACLF) is an acute liver decompensation in cirrhotic patients, which leads to organ failures and high short-term mortality. The treatment is based on the management of complications and, in severe cases, liver transplantation. Since specific treatment is unavailable, we aimed to evaluate the safety and initial efficacy of bone marrow mesenchymal stem cells (BM-MSC) in patients with ACLF Grades 2 and 3, a population excluded from previous clinical trials. Methods: This is a randomized placebo-controlled phase I-II single center study, which enrolled 9 cirrhotic patients from 2018 to 2020, regardless of the etiology. The control group (n=5) was treated with standard medical therapy (SMT) and placebo infusion of saline. The intervention group (n=4) received SMT plus 5 infusions of 1 × 10^6 cells/kg of BM-MSC for 3 weeks. Both groups were monitored for 90 days. A Chi-square test was used for qualitative variables, and the t-test and Mann–Whitney U test for quantitative variables. The Kaplan–Meier estimator was used to build survival curves. In this study, we followed the intention-totreat analysis, with a significance of 5%. Results: Nine patients with a mean Child–Pugh (CP) of 12.3, MELD of 38.4, and CLIF-C score of 50.7 were recruited. Hepatitis C and alcohol were the main etiologies. )e average infusion per patient was 2.9 and only 3 patients (2 in control and 1 in the BM-MSC group) received all the protocol infusions. There were no infusion-related side effects, although one patient in the intervention group presented hypernatremia and a gastric ulcer, after the third and fifth infusions, respectively. )e survival rate after 90 days was 20% (1/5) for placebo versus 25% (1/4) for the BM-MSC. The patient who completed the entire MSC protocol showed a significant improvement in CP (C-14 to B-9), MELD (32 to 22), and ACLF (grade 3 to 0). Conclusion: BM-MSC infusion is safe and feasible in patients with ACLF Grades 2 and 3

Resultados da terapia dupla (interferon e ribavirina) para hepatite C em um centro de referência no sul do Brasil: um estudo da vida real

Introdução: A Hepatite C tem uma prevalência estimada em cerca de 170 milhões de pessoas mundialmente e cursa com grande morbimortalidade. O tratamento deste vírus tem se alterado significativamente nos últimos anos, porém, no Brasil, ainda imperam os tratamentos baseados em interferon convencional ou interferon-peguilado associado à ribavirina. Métodos: estudo de coorte, retrospectivo, conduzido no Hospital de Clínicas de Porto Alegre. Foram incluídos 237 pacientes com Hepatite C tratados com interferon e ribavirina ou interferon-peguilado e ribavirina Resultados: A taxa global de resposta virológica sustentada obtida foi de 33,33%, sendo 37,93% nos pacientes com regime baseado no interferon convencional e 32,69% nos com interferon-peguilado. A análise demonstrou uma maior taxa de resposta virológica sustentada entre os pacientes que apresentaram, à análise genética, expressão CC do polimorfismo da IL 28B. Palavras-chave: Hepatite C; interferon; resposta virológica sustentad

Resultados da terapia dupla (interferon e ribavirina) para hepatite C em um centro de referência no sul do Brasil: um estudo da vida real

Introdução: A Hepatite C tem uma prevalência estimada em cerca de 170 milhões de pessoas mundialmente e cursa com grande morbimortalidade. O tratamento deste vírus tem se alterado significativamente nos últimos anos, porém, no Brasil, ainda imperam os tratamentos baseados em interferon convencional ou interferon-peguilado associado à ribavirina.Métodos: estudo de coorte, retrospectivo, conduzido no Hospital de Clínicas de Porto Alegre. Foram incluídos 237 pacientes com Hepatite C tratados com interferon e ribavirina ou interferon-peguilado e ribavirinaResultados: A taxa global de resposta virológica sustentada obtida foi de 33,33%, sendo 37,93% nos pacientes com regime baseado no interferon convencional e 32,69% nos com interferon-peguilado. A análise demonstrou uma maior taxa de resposta virológica sustentada entre os pacientes que apresentaram, à análise genética, expressão CC do polimorfismo da IL 28B.Palavras-chave: Hepatite C; interferon; resposta virológica sustentad

Hepcidin serum levels in HCV chronically mono-infected naïve patients, compared to healthy individuals

Introduction: Metabolism of iron is altered in patients infected with chronically Hepatitis C. The aim of this study is to compare compare the hepcidin levels in between individuais chronically infected with HCV and uninfected individuals. The aim of this study is to compare the hepcidin serum levels between individuals chronically infected with HCV and uninfected individuals. Methods: A cross-sectional study evaluating hepcidin serum levels of mono-infected HCV (n=29), naive, non-diabetic, non-cirrhotic and non-obese patients by means of ELISA, compared to uninfected patients (n=9) with the same characteristics. The degree of liver fibrosis, according to the METAVIR scale on liver biopsies, the lipid profile, the resistance insulin level, as calculated on HOMA-IR (homeostatic model assessment for insulin resistance), the interleukin-6 (IL-6) and the ferritin serum levels were also measured. Results: The levels of hepcidin were significantly lower in HCV patients compared to controls (8.4 pg/mL (±4.94) vs. 19.51 pg/mL (±5.51)) with p<0.001. The levels of ferritin and hepcidin did not show any relation. There was no difference between hepcidin levels in relation to viral genotype, viral load, IL-6 and degrees of fibrosis within HCV infected individuals. Conclusion: It is possible that hepatic iron overload in this population is explained by suppressed levels of hepcidin in patients with HCV. Keywords: Hepcidin; HCV; interleukin-6 (IL-6); mono-infecte

Serum markers of apoptosis and inflammation in patients with chronic hepatitis C virus

Background: Our study aimed to elucidate the possible relationship between apoptosis, inflammation, and fibrosis in hepatitis C virus (HCV) patients. Methods: Patients aged 18 to 60 years with HCV were included and underwent clinical and pathological examinations. Patients with chronic renal failure, malignancies, alcohol abuse, or pregnancy and/or those who were taking immunosuppressant agents were excluded. Body mass index, glucose, insulin, HOMA-IR, lipid profile, and the extent of fibrosis (METAVIR) were determined, as were the serum levels of CK-18 (M30-Apoptosense, ELISA - Lausen, Switzerland), Fas, Fas-L, I-CAM, V-CAM, MIF, and PAI (HSEP-63k, Milliplex, Millipore, Copenhagen, Denmark). Results: Of the 55 patients, 23 were treatment-naïve, 15 demonstrated a sustained virologic response (SVR) and 17 were non-responders (NR). The levels of CK-18 did not differ between the groups. Inflammation, as assessed by sVCAM, was directly associated with advanced fibrosis (p = 0.009). sFas-L and sVCAM were increased in the SVR group compared with the treatment-naïve group (p = 0.006 and 0.019, respectively). sVCAM was associated with both sFas-L (rs = 0.778, p < 0.001) and MIF (rs = 0.621, p < 0.001). MIF and sFas-L were also correlated (rs = 0.526, p = 0.001). Conclusions: Advanced fibrosis was positively correlated with inflammation according to the levels of sVCAM. Furthermore, apoptosis, as assessed by the levels of sFas-L, and inflammation, as determined by sVCAM, were increased in the patients who achieved viral clearance compared with the treatment-naïve patients. The patients with advanced fibrosis were also more likely to present with higher levels of MIF

Randomized double-blind clinical trial of a new human epoetin versus a commercially available formula for anemia control in patients on hemodialysis

OBJECTIVES: Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation). METHODS: The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians’ discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495. RESULTS: The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9¡1.2 and 10.96¡1.2 g/dL (p = 0.89) in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar. CONCLUSIONS: The epoetin formulations tested in this study are equivalent in efficacy and safety