Intrahepatic Cholangiocarcinoma, Associated with Anti-hepatitis C Virus Positive Liver Cirrhosis A Case Report

Abstract Purpose Ledipasvir/sofosbuvir is an oral combination therapy containing fixed doses of direct-acting antiviral agents indicated for the treatment of hepatitis C virus (HCV) infection. Currently there are limited data on the clinical efficacy of crushed ledipasvir/sofosbuvir administered via feeding tube. Summary This case report discusses the successful treatment of chronic HCV genotype 1b infection with crushed ledipasvir/sofosbuvir administered through a percutaneous endoscopic gastrostomy (PEG) tube in a patient with human immunodeficiency virus (HIV) coinfection and high-grade sarcoma who had severe swallowing difficulties. The patient received crushed ledipasvir/sofosbuvir daily for a total of 12 weeks. At 12 weeks the patient had achieved a sustained virologic response. Conclusion Currently, ledipasvir/sofosbuvir is available only as a tablet, with limited pharmacokinetic data available to guide clinicians on use of the fixed-dose combination medication in crushed form. This case report highlights our experience treating a patient with HCV/HIV coinfection through administration of crushed ledipasvir/sofosbuvir via PEG tube, which we found to be a safe and effective therapeutic option.

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Enhanced immune responses, PI3K/AKT and JAK/STAT signaling pathways following hepatitis C virus eradication by direct-acting antiviral therapy among Egyptian patients: a case control study

Pathogens and Disease ◽

10.1093/femspd/ftab008 ◽

2021 ◽

Author(s):

Haidi Karam-Allah Ramadan ◽

Gamal Badr ◽

Nancy K Ramadan ◽

Aml Sayed

Keyword(s):

Immune Response ◽

Liver Cirrhosis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Immune Responses ◽

Signaling Pathways ◽

Liver Diseases ◽

Stat Signaling ◽

Chronic Hcv ◽

Direct Acting

Abstract The use of direct-acting antivirals (DAAs) therapy for the treatment of hepatitis C virus (HCV) results in a high sustained virological response (SVR) and subsequently alters liver immunologic environment. However, hepatocellular carcinoma (HCC) may occur after DAAs treatment. We aimed to clarify changes of immune responses, PI3K/AKT and JAK/STAT signaling pathways in HCV-induced liver diseases and HCC following DAAs treatment. Four cohorts are classified as chronic HCV patients, HCV-related cirrhosis without HCC, HCV-related cirrhosis and HCC, and healthy control group. The patient groups were further divided into treated or untreated with DAAs with SVR12. Increased percentages of CD3, CD8 and CD4, decreased CD4/FoxP3/CD25, CD8/PD-1 and CD19/PDL-1 were found in DAAs-treated patients in the three HCV groups. Following DAAs therapy, the levels of ROS, IL-1β, IL-6, IL-8 and TNF-α were significantly decreased in the three HCV groups. Treated HCV patients showed up regulation of p-AKT and p-STAT5 and down regulation of p-STAT3, HIF-1α and COX-2. In conclusion, DAAs enhance the immune response in chronic HCV and liver cirrhosis, hence our study is the first to show change in PI3K/AKT and JAK/STAT signaling pathways in different HCV-induced liver diseases after DAAs. In chronic HCV, DAAs have better impact on the immune response while in liver cirrhosis not all immune changes were prominent.

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Idenix v. Gilead: The enablement and written description limits of a genus claim

Journal of Generic Medicines The Business Journal for the Generic Medicines Sector ◽

10.1177/17411343211013572 ◽

2021 ◽

Vol 17 (2) ◽

pp. 77-83

Author(s):

Keith A Zullow ◽

Cindy Chang ◽

Sean Anderson

Keyword(s):

Case Report ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Supreme Court ◽

The Supreme Court ◽

Federal Circuit ◽

Written Description ◽

Insufficient Number

In Idenix Pharms. LLC v. Gilead Sci. Inc., 941 F.3d 1149 (Fed. Cir. 2019), the Federal Circuit affirmed a judgment of invalidity of a patent claiming methods for treating Hepatitis C virus for, inter alia, lack of enablement. The Supreme Court denied Idenix’s petition for a writ of certiorari, meaning that the Federal Circuit decision stands, and genus claims covering thousands of compounds that were supported by an insufficient number of examples have failed the enablement test not once, but twice. See Wyeth & Cordis Corp. v. Abbott Labs., 720 F.3d 1380 (Fed. Cir. 2013). This case report presents the context surrounding the Federal Circuit’s Idenix decision and the Supreme Court’s decision not to hear the case.

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