Hepatitis C Treatment in Elderly Patients

The patients with chronic hepatitis C (CHC) are getting older and the demands for treatment to those patients are increasing due to the high risk of development of hepatocellular carcinoma. Elderly patients were previously defined as 60 years and over, however definition of the elderly patients shifted to be older year to year. Interferon (IFN) and ribavirin combination therapy was significantly improved efficacy of treatment, however ribavirin induces anemia, resulted in lower efficacy due to reduction of ribavirin for the elderly patients. And efficacy of over 60 years old was comparable to the patients under 60 years. In the CHC patients with genotype 1, the efficacy of elderly patient was significantly lower than that of younger patients, especially in female. Direct-acting antivirals (DAAs) therapy makes treatment efficacy improved to over 90% and side effect of treatment was dramatically reduced compared to IFN-based therapy. The efficacy of dual oral therapy by using asunaprevir (ASV) and daclatasvir (DCA) for elderly patients with hepatitis C virus (HCV) genotype 1b has not been fully clarified. In this article we would like to show the efficacy of elderly patients with CHC, especially patients infected with genotype 1b, from the era of IFN monotherapy to the era of new DAAs

The Hypervariable Region 1 Protein of Hepatitis C Virus Broadly Reactive with Sera of Patients with Chronic Hepatitis C Has a Similar Amino Acid Sequence with the Consensus Sequence

AbstractHypervariable region 1 (HVR1) proteins of hepatitis C virus (HCV) have been reported to react broadly with sera of patients with HCV infection. However, the variability of the broad reactivity of individual HVR1 proteins has not been elucidated. We assessed the reactivity of 25 different HVR1 proteins (genotype 1b) with sera of 81 patients with HCV infection (genotype 1b) by Western blot. HVR1 proteins reacted with 2–60 sera. The number of sera reactive with each HVR1 protein significantly correlated with the number of amino acid residues identical to the consensus sequence defined by Puntoriero et al. (G. Puntoriero, A. Lahm, S. Zucchelli, B. B. Ercole, R. Tafi, M. Penzzanera, M. U. Mondelli, R. Cortese, A. Tramontano, G. Galfre', and A. Nicosia. 1998. EMBO J. 17, 3521–3533.) (r = 0.561, P < 0.005). The most widely reactive HVR1 protein, 12-22, had a sequence similar to the consensus sequence. The peptide with C-terminal 13-amino-acids sequence of HVR1 protein 12-22 (NH2-CSFTSLFTPGPSQK) was injected into rabbits as an immunogen. The rabbit immune sera reacted with 9 of 25 HVR1 proteins of genotype 1b including HVR1 protein 12-22 and with 3 of 12 proteins of genotype 2a. These results indicate that the HVR1 protein broadly reactive with patients' sera has a sequence similar to the consensus sequence, can induce broadly reactive sera, and could be one of the candidate immunogens in a prophylactic vaccine against HCV

Impact of HBV Infection on Outcomes of Direct-Acting Antiviral Therapy of Chronic Hepatitis C

Background: Most clinical trials of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection have excluded hepatitis B virus (HBV) coinfection, and little is known about the effects of DAA on chronic hepatitis C patients with HBV coinfection. Recent studies have reported that DAA therapy for HCV can also cause HBV reactivation in patients with HBV and HCV coinfection. The aim of this study was to assess the effects of DAA on sustained virologic response (SVR) and HBV reactivation in patients with chronic hepatitis C. Methods: Participants comprised 199 chronic hepatitis C patients who received DAA therapy (96 men, 103 women; mean age, 66.7 ± 12.0 years). Results: Twelve patients were coinfected with HCV and HBV. Sixty patients were HBV surface antigen negative but positive for hepatitis B core antibody and/or hepatitis B surface antibody, and one hundred and twenty-seven patients had not been exposed to HBV. Rates of SVR in HBV and HCV coinfected patients, HBV prior infection, and no exposure to HBV were 100, 95, and 97%, respectively. Significant differences were seen between each group. No case showed HBV reactivation. Conclusions: DAA treatments were effective in patients with HBV coinfection or HBV prior infection, as well as HCV monoinfection. As the number of cases was small, we still suggest caution regarding HBV reactivation in HCV and HBV coinfected patients undergoing treatment with DAA

Análisis de las comorbilidades en pacientes con colitis ulcerosa: una herramienta para prevenir las exacerbaciones en casos de colitis ulcerosa

There have been previous studies, especially in Western countries and even in some areas in Asia, about extra-intestinal manifestations (EIMs) and its link with the outcome of inflammatory bowel disease (IBD), which includes Crohn’s disease (CD), and ulcerative colitis (UC). This link is crucial when discussing a patient’s prognosis and important when dealing with UC management. The aim of this study was to clarify the most common comorbidities associated with UC, emphasizing immunologic comorbidities in Japan. This study was a retrospective analysis performed at Nagoya University Hospital. The data collection started in March, 2019, and continued for two years. We retrieved the medical records of 105 patients with UC diagnosis, from which the data of 176 EIMs were extracted and analyzed. Results showed that EIMs with UC in the active phase accounted for 43.7% of total EIMs. Twenty-six patients with immune-mediated inflammatory disease frequently had an active phase (odds ratio [OR] 3.84, 99% CI, 1.44–10.27). Comorbidities showing an active manifestation of symptoms and UC in the active phase were significantly correlated in patients with immunological comorbidities, such as peripheral arthritis (r = 0.97, p < 0.01) and rheumatoid arthritis (RA) (r = 0.99, p < 0.01), as well as in patients with primary sclerosis cholangitis (PSC) (r = 0.98, p < 0.01). In conclusion, this analysis suggests the importance of having full comprehension of how immunological comorbidities affect the natural development of UC, which is of vital importance to prevent further UC complications and properly adjust the management of the disease.Se trata de un análisis retrospectivo que estudia múltiples comorbilidades de índole inmunológico que se da en pacientes con colitis ulcerosa. Este estudio se llevó a cabo en el hospital universitario de la Universidad de Nagoya. Se recolectó datos de 105 pacientes con colitis ulcerosa, de los cuales 176 comorbilidades extraintestinales fueron analizadas. Se encontró que comorbilidades con manifestación activa de síntomas y con colitis ulcerosa en fase activa fueron significativamente correlacionadas en pacientes con comorbilidades inmunológicas, tales como artritis periféricas (r=O.97, P<O.OI ), artritis reumatoide (r=O.99, P<O.OI ), así como pacientes con colangitis esclerosa primaria (r=O.98, P<O.OI ). En conclusión, este análisis sugiere la importancia de tener plena comprensión de cómo las comorbilidades inmunológicas afectan el desarrollo natural de la colitis ulcerosa, lo cual es de vital importancia para prevenir mayores complicaciones de la colitis ulcerosa y ajustar adecuadamente el manejo de la enfermedad.Japón. Ministerio de Educación, Cultura, Deportes, Ciencia y Tecnología (Monbukagakusho)Artículo de investigació

Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis

Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes

Secreted Ectodomain of SIGLEC-9 and MCP-1 Synergistically Improve Acute Liver Failure in Rats by Altering Macrophage Polarity

Effective treatments for acute liver failure (ALF) are still lacking. We recently reported that a single intravenous administration of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) into the D-galactosamine (D-Gal)-induced rat ALF model improves the liver injury. However, the specific factors in SHED-CM that are responsible for resolving ALF remain unclear. Here we found that depleting SHED-CM of two anti-inflammatory M2 macrophage inducers—monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acidbinding Ig-like lectin-9 (sSiglec-9)—abolished its ability to resolve rat ALF. Furthermore, treatment with MCP-1/sSiglec-9 alone dramatically improved the survival of ALF rats. This treatment induced anti-inflammatory M2, suppressed hepatocyte apoptosis, and promoted hepatocyte proliferation. Treatment with an M2-depletion reagent (mannosylated clodronate liposomes) suppressed the recovery. In addition, MCP-1 and sSiglec-9 synergistically promoted the M2 differentiation of bone marrow-derived macrophages via CCR2, accompanied by the production of multiple liver-regenerating factors. The conditioned medium from MCP-1/sSiglec-9-activated M2 macrophages, but not from interleukin-4-induced ones, suppressed the D-Gal- and LPS-induced apoptosis of primary hepatocytes and promoted their proliferation in vitro. The unique combination of MCP-1/sSiglec-9 ameliorates rat ALF by inhibiting hepatocellular apoptosis and promoting liver regeneration through the induction of anti-inflammatory/tissue-repairing M2 macrophages

Development of a novel delivery quality assurance system based on simultaneous verification of dose distribution and binary multi-leaf collimator opening in helical tomotherapy

Abstract Background Intensity-modulated radiation therapy (IMRT) requires delivery quality assurance (DQA) to ensure treatment accuracy and safety. Irradiation techniques such as helical tomotherapy (HT) have become increasingly complex, rendering conventional verification methods insufficient. This study aims to develop a novel DQA system to simultaneously verify dose distribution and multi-leaf collimator (MLC) opening during HT. Methods We developed a prototype detector consisting of a cylindrical plastic scintillator (PS) and a cooled charge-coupled device (CCD) camera. Scintillation light was recorded using a CCD camera. A TomoHDA (Accuray Inc.) was used as the irradiation device. The characteristics of the developed system were evaluated based on the light intensity. The IMRT plan was irradiated onto the PS to record a moving image of the scintillation light. MLC opening and light distribution were obtained from the recorded images. To detect MLC opening, we placed a region of interest (ROI) on the image, corresponding to the leaf position, and analyzed the temporal change in the light intensity within each ROI. Corrections were made for light changes due to differences in the PS shape and irradiation position. The corrected light intensity was converted into the leaf opening time (LOT), and an MLC sinogram was constructed. The reconstructed MLC sinogram was compared with that calculated using the treatment planning system (TPS). Light distribution was obtained by integrating all frames obtained during IMRT irradiation. The light distribution was compared with the dose distribution calculated using the TPS. Results The LOT and the light intensity followed a linear relationship. Owing to MLC movements, the sensitivity and specificity of the reconstructed sinogram exceeded 97%, with an LOT error of − 3.9 ± 7.8%. The light distribution pattern closely resembled that of the dose distribution. The average dose difference and the pass rate of gamma analysis with 3%/3 mm were 1.4 ± 0.2% and 99%, respectively. Conclusion We developed a DQA system for simultaneous and accurate verification of both dose distribution and MLC opening during HT