Chronic hepatitis C and chronic kidney disease: Advances, limitations and unchartered territories.

Over the past few years, treatment options for chronic hepatitis C virus (HCV) infection have evolved dramatically. The current approved interferon-free direct-acting antiviral (DAA) regimens have been shown to be safe and effective with sustained virologic response (SVR) rates of >90% in most patients. Unique issues yet remain such as the challenges in patients with impaired renal function or decompensated cirrhosis. Patients with stages 4-5 chronic kidney disease (CKD) have a higher prevalence of HCV infection compared with the general population. Chronic HCV in those on dialysis and in kidney transplant recipients is associated with higher morbidity and mortality than uninfected patients. The HCV-infected population is also at risk of developing extrahepatic manifestations associated with altered immune system function and chronic inflammation with cryoglobulinaemic vasculitis being the most common of these manifestations. Therefore, patients with CKD stages 4-5 have to be considered priority patients for HCV therapy. New antiviral therapies have the potential to improve outcomes in this vulnerable patient population, including those on haemodialysis. Recently published studies conducted in kidney transplant recipients have demonstrated successful outcomes. It is thus essential that we carefully select the most appropriate DAA regimen and the best time for treatment in the context of kidney transplantation or cryoglobulinaemic vasculitis. While sofosbuvir, the only approved nucleotide NS5B inhibitor, has been the backbone of most pangenotypic therapeutic regimens, it has a limitation in those with advanced kidney disease. The currently approved regimens for those with stage 4/5 CKD, while effective, have challenges in that they apply to genotype 1/4 and may require RBV for genotype 1a. Globally, genotype 3 is a common infection, and thus, this group with CKD presents a huge unmet need for effective therapies. As therapy of HCV in renal transplant recipients has been highly successful, it provides an opportunity to expand the use of HCV-infected organs in solid organ transplantation.

Donor hemosiderosis does not affect liver function and regeneration in the setting of living donor liver transplantation.

Living donor liver transplantation (LDLT) demands a careful assessment of abnormal findings discovered during the evaluation process to determine if there will be any potential risks to the donor or recipient. Varying degrees of elevated hepatic iron levels are not uncommonly seen in otherwise healthy individuals. We questioned whether mild expression of hemosiderin deposition presents a safety concern when considering outcomes of living donation for both the donor and the recipient. We report on three LDLT patients who were found to have low- to moderate-grade hemosiderin deposition on liver biopsy. All other aspects of their evaluation proved satisfactory, and the decision was made to proceed with donation. There were no significant complications in the donors, and all demonstrated complete normalization of liver function postoperatively, with appropriate parenchymal regeneration. The recipients also had unremarkable postoperative recovery. We conclude that these individuals can be considered as potential donors after careful evaluation.

Histological changes in ovaries of mice exposed to butea monosperma: preliminary study / Cambios histológicos en ovarios de ratón expuestos a butea monosperma: estudio preliminar

In Ayurvedic practice Butea monosperma (Palash) is in clinical use for hundreds of years as a contraceptive. Seeds of Butea monosperma are also used as an anthelmitic (Ansani et al., 1979) and antimicrobial (Avirutnant & Pongpan, 1983). Butea monosperma (Fabaceae family) locally known as Palash (Dhak) if given for 3 consecutive days acts as an antifertility agent for which it has been is traditionally used since time immemorial. The objective of the present study was to search the effect of Butea monosperma seeds on the ovary of mice. Observations in the present study were massive degeneration of ova in almost all the follicles, irrespective of the stage of their development. The ova from treated animals showed different stages of necrotic process. Moreover, the arrangement of follicular cells was also disturbed. The Palash seeds in the form of powder when administered orally with distilled water, according to the body weight i.e.2g/Kg, of female mice, for three consecutive days showed notable changes in ovaries. The animals were sacrificed on day next to the last day of treatment and ovaries were extirpated. Ovaries studied histologically after Haematoxylin & Eosin staining showed most of the follicle in immature state with undefined nucleus and nucleoli in the ovum. Others showed degenerative changes in the ovum. Follicles had lost their normal shape and arrangement and organization of granulosa cells. It was conspicuous to find that almost all follicles including graafian follicles of treated ovaries were undergoing degenerative changes simultaneously. The rate of apoptosis in the granulosa cells when studied was found increased in treated cases as compared with control. The study suggests that the disintegration of ova in the ovaries is a specific effect of Butea monosperma seed administration.

En la práctica Ayurvédica Butea monosperma (Palash) se encuentra en uso clínico durante cientos de años como método anticonceptivo. Semillas de Butea monosperma también se utilizan como un antihemético y antimicrobiano. Butea monosperma (familia Fabaceae) conocida localmente como Palash (Dhak) si se administra durante 3 días consecutivos actúa como un agente anticonceptivo que se utiliza tradicionalmente desde tiempos inmemoriales. El objetivo del presente estudio fue buscar el efecto de las semillas de Butea monosperma en ovarios de ratones. Se obsevó degeneración masiva de los óvulos en casi todos los folículos, independientemente de la fase de su desarrollo. Los óvulos de los animales tratados mostraron las diferentes etapas del proceso necrótico. Por otra parte, la disposición de las células foliculares se mostró alterada. El polvo de semillas de Palash, cuando se administra a los ratones, por vía oral en agua destilada, i.e. 2g/Kg peso corporal, durante tres días produce cambios en los ovarios. Los animales se sacrificaron al día siguiente terminado el tratamiento y fueron extirpados los ovarios. Los ovarios se estudiaron histológicamente con HE mostrándose la mayoría de los folículos en estado inmaduro, con núcleo definido y nucléolos en el óvulo. Otros mostraron cambios degenerativos en los óvulos. Los folículos habían perdido su forma normal y la disposición y organización de células de la granulosa. Se encontró que casi todos los folículos incluyendo los folículos mostraban cambios degenerativos de manera simultánea. En los casos tratados, la tasa de apoptosis en las células de la granulosa estaba aumentada, en comparación con el grupo control. El estudio sugiere que la desintegración de los óvulos en los ovarios es un efecto específico de la administración de las semillas de Butea monosperma.