Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model

Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg-1·day-1 by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.

Treatment-resistant depression increases health costs and resource utilization / Depressão resistente ao tratamento aumenta os custos e utilização de recursos

OBJECTIVE: Major Depressive Disorder (MDD) is a debilitating condition with a marked social impact. The impact of MDD and Treatment-Resistant Depression (TRD+) within the Brazilian health system is largely unknown. The goal of this study was to compare resource utilization and costs of care for treatment-resistant MDD relative to non-treatment-resistant depression (TRD-). METHODS: We retrospectively analyzed the records of 212 patients who had been diagnosed with MDD according to the ICD-10 criteria. Specific criteria were used to identify patients with TRD+. Resource utilization was estimated, and the consumption of medication was annualized. We obtained information on medical visits, procedures, hospitalizations, emergency department visits and medication use related or not to MDD. RESULTS: The sample consisted of 90 TRD+ and 122 TRD- patients. TRD+ patients used significantly more resources from the psychiatric service, but not from non-psychiatric clinics, compared to TRD- patients. Furthermore, TRD+ patients were significantly more likely to require hospitalizations. Overall, TRD+ patients imposed significantly higher (81.5%) annual costs compared to TRD- patients (R$ 5,520.85; US$ 3,075.34 vs. R$ 3,042.14; US$ 1,694.60). These findings demonstrate the burden of MDD, and especially of TRD+ patients, to the tertiary public health system. Our study should raise awareness of the impact of TRD+ and should be considered by policy makers when implementing public mental health initiatives.

OBJETIVO: O Transtorno Depressivo Maior (TDM) é uma condição debilitante com um forte impacto social. O impacto do TDM e Depressão Resistente ao Tratamento (DRT+) no sistema de saúde brasileiro é praticamente desconhecido. Nosso objetivo é comparar a utilização de recursos e custos dos cuidados para o tratamento de DRT+ em relação ao TDM não resistente (DRT-). MÉTODOS: Foram analisados retrospectivamente os prontuários de 212 pacientes diagnosticados com TDM segundo a CID-10. Critérios específicos foram utilizados para identificar pacientes com DRT+. A utilização dos recursos foi estimada e consumo de medicamentos foram anualizados. Foram obtidas informações sobre consultas, procedimentos, internações, atendimentos no serviço de emergência e uso de medicação relacionada ou não ao TDM. RESULTADOS: A amostra foi composta de 90 pacientes DRT+ e 122 DRT-. Pacientes DRT+ utilizaram significativamente mais recursos do serviço de psiquiatria, mas não em clínicas não psiquiátricas, em relação a DRT-. Eles eram significativamente mais propensos a exigir internações. Pacientes DRT+ apresentaram um custo direto anual significativamente maior (81,5%) do que pacientes com depressão não resistente (R$ 5.520,85; US$ 3.075,34 contra R$ 3.042,14, US$ 1.694,60). Estes resultados demonstram o impacto do TDM, principalmente da DRT+ ao sistema de saúde público terciário. Nosso estudo deve aumentar a sensibilização para o impacto da DRT + e deve ser considerado pelos formuladores de políticas públicas na implementação de iniciativas de saúde mental.