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Following the advent of direct-acting antivirals (DAAs), the treatment of hepatitis C virus (HCV) infection is now rarely challenging. However, data are still limited concerning DAA use in patients affected by glucose-6-phosphate dehydrogenase deficiency (G6PDd). Based on these considerations, the goal of this study was to evaluate the effectiveness and safety of DAAs in this subpopulation. A retrospective multicenter observational study (2015–2023) was conducted on all 2754 consecutive HCV-positive patients treated with first- and second-generation all-oral DAAs, and with a G6PDd diagnosis confirmed by quantitative testing (n = 38). At the treating clinician's discretion, an enhanced clinical and laboratory follow-up was performed, generally on a monthly basis both during treatment and up to six months after the end of it. Concerning hematochemical parameters, no significant differences were found between any considered time point. In all cases, no treatment-related adverse events were reported, and virologic response rates were as expected without G6PDd. In conclusion, in a large experience which, to the best of our knowledge, is unprecedented in the literature, the treatment of HCV hepatitis with nearly all available DAAs in patients with G6PDd as a comorbidity—a common occurrence in countries such as Italy—proved to be highly effective and safe. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is a global health problem that presents as a spectrum of liver disease, reflecting an interplay between the virus and the host immune system. HBV genomes exist as episomal covalently closed circular DNA (cccDNA) or chromosomal integrants. The relative contribution of these genomes to the viral transcriptome in chronic hepatitis B (CHB) is not well-understood. We developed a qPCR method to estimate the abundance of HBV cccDNA- and integrant-derived viral transcripts and applied this to a cohort of patients diagnosed with CHB in the HBe antigen negative phase of disease. We noted a variable pattern of HBV transcripts from both DNA templates, with preS1/S2 mRNAs predominating and a significant association between increasing age and the expression of integrant-derived mRNAs, but not with inflammatory status. In contrast, cccDNA-derived transcripts were associated with markers of liver inflammation. Analysis of the inflammatory hepatic transcriptome identified 24 genes significantly associated with cccDNA transcriptional activity. Our study uncovers an immune gene signature that associates with HBV cccDNA transcription and increases our understanding of viral persistence. [ABSTRACT FROM AUTHOR]

Background To verify whether, as index of insulin resistance, ISI-gly (insulin sensitivity index) is more efficient than HOMA-IR (homeostatic model assessment) or QUICKI (quantitative insulin sensitivity check index) in detecting patients with the metabolic syndrome. Methods Excluding patients with known diabetes, endocrine, liver and kidney diseases, we enrolled 553 subjects who were screened for metabolic abnormalities. After 5 days of a balanced weight maintenance diet, we performed an OGTT (oral glucose tolerance test) and measured fasting and 2-h postload blood sugar and insulin, from which we calculated ISI-gly, HOMA-IR and QUICKI, stratifying patients in tertiles. Statistical comparisons were performed for a number of metabolic variables between tertiles of the same index, as well as between tertiles of different indexes presumably expressing identical insulin resistance. Results All variables reflecting the metabolic syndrome were significantly more altered in the top as compared to the intermediate and the lowest tertile for HOMA-IR, the opposite for ISI-gly. Comparing homologous measurements of the top tertile of HOMA-IR with the lowest tertile of ISI-gly (presumably expressing identical insulin resistance), fasting glucose and insulin were significantly higher, while 2-h OGTT values were significantly lower. The opposite occurred comparing the lowest HOMA-IR to the highest ISI-gly tertile, the diagnostic predictive values of the latter in detecting metabolic derangements being also higher. Data from QUICKI 1st to 3rd tertiles exactly matched those obtained from HOMA-IR 3rd to 1st tertile. Conclusions ISI-gly, which includes postload glucose and insulin concentrations, provides a more accurate estimate of whole-body insulin sensitivity than HOMA-IR or QUICKI, derived from fasting measurements only, thus constituting a more sensitive tool for screening and preventing metabolic abnormalities. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a major public health problem around the world and it is estimated that there are about 200 million infections globally. The majority of HCV infected patients develop chronic infection, which can progress to liver cirrhosis, hepatocellular carcinoma, and liver failure. Since the discovery of the virus in 1989, impressive progress has been made in the treatment of HCV hepatitis. However, the actual standard of care in treating HCV infection, represented by the combination therapy of pegylated interferon alpha 2a or 2b with ribavirin, fails to cure near half of treated patients. This paper aimed to trace a brief overview of the progress made by interferon-based treatments for HCV hepatitis since their introduction in the early 1990s, and to highlight the results of recent clinical studies concerning new and emerging drugs.

Idenix Pharmaceuticals Inc and Novartis AG are codeveloping valopicitabine dihydrochloride, a once-daily oral nucleoside for the potential treatment of HCV infection. In January 2005, a phase IIa clinical trial comparing valopicitabine dihydrochloride with pegylated IFN in treatment-naive HCV patients was ongoing, in addition to a phase IIb trial in patients that had previously failed pegylated IFN and ribavirin combination therapy. In January 2006, an international phase III trial in treatment-refractory patients was planned for the first half of the year, with a phase III trial in treatment-naive individuals planned for the second half of the year.