Discovery Chemistry, Bristol-Myers Squibb, Route 141 and Henry Clay Road, Wilmington, DE 19880, USA.
Published: March 2003
AI Article Synopsis
Article Abstract
Starting from a hexapeptide boronic acid lead, 3-amino bicyclic pyrazinones as novel beta-sheet dipeptide mimetics have been designed and synthesized. Side-chain manipulation of this scaffold generated a series of potent, nonpeptidic inhibitors of HCV NS3 protease.
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address:
Background: Hepatitis C virus (HCV) resistance-associated substitutions (RASs) have a significant impact on the treatment of HCV with direct-acting antivirals (DAAs). However, limited research has been conducted, and no standardized methods for detecting RASs in mainland China.
Objectives: To develop and apply a novel method for detecting HCV RASs in HCV RNA-positive patients in Linzhou, China.
Introduction: The rate of acute hepatitis C increased by 7% between 2020 and 2021, after the number of cases doubled between 2014 and 2020. With the current adoption of pan-genotypic HCV therapy, there is a need for improved availability and accessibility of this therapy. However, double and triple DAA-resistant variants have been identified in genotypes 1 and 5 with resistance-associated amino acid substitutions (RAASs) in NS3/4A, NS5A, and NS5B.
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is associated with major risk factors such as hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic fatty liver disease, and metabolic dysfunction-associated steatotic liver diseases. Despite the recent progress in systemic treatment regimens involving immunotherapies and targeted therapeutics, advanced HCC remains difficult to control. Moreover, with several treatment modalities currently available for HCC such as radiation therapy, transarterial chemoembolization (TACE), checkpoint immunotherapies, and multi-tyrosine kinase inhibitors, it is unclear what combination yields the greatest treatment efficacy and durability.
* A meta-analysis of 55 studies involving 7,180 HCC patients indicated that HBV infection did not significantly affect overall survival (OS) or progression-free survival (PFS) with ICIs, but HBV-infected patients may have a better tumor response.
* High baseline HBV load is linked to worse survival outcomes, while antiviral therapy demonstrates improved prognostic outcomes for HCC patients treated with ICIs.
Lenvatinib, a multi-target inhibitor of receptor tyrosine kinases, has been increasingly used in the treatment of advanced hepatocellular carcinoma (HCC). However, its association with renal adverse effects, including proteinuria and renal microvascular complications, was not fully understood in HCC patients. We reported a case of a 68-year-old male with a history of hypertension, diabetes mellitus, and hepatitis C virus (HCV) infection, diagnosed with primary HCC in 2015.
