Τόμος 28 (2014) – Τεύχος 3 – Άρθρο 1- Review of Clinical Pharmacology and Pharmacokinetics-Διεθνής Έκδοση – Volume 28 (2014) – Issue 3 – Article 1 – Review of Clinical Pharmacology and Pharmacokinetics -International Edition

Μακροπρόθεσμη Προστατευτική Δράση της Υποστηρικτικής Θεραπείας με Χλωριούχο Αμμώνιο από το Ηπατοτοξικό Αποτέλεσμα της Ηπατίτιδας C –
Long-term Protective Action of Ammonium Chloride Supportive Therapy from the Hepatotoxic Effect of Hepatitis C Infection

Lambrou C., Kouskoukis K., KiassosD.: Long-term Protective Action of Ammonium Chloride Supportive Therapy from the Hepatotoxic Effect of Hepatitis C Infection, Rev. Clin. Pharmacol. Pharmacokinet. Int. Ed. 28: 77-83 (2014)

Αγγλικά – English

 Κλινική Μελέτη
Clinical Trial

   Liver infection with hepatitis C virus will become a chronic infection in up to 85% of the infected persons. Less than 27% of HCV relapsing patients achieve a sustained virological response after the standard treatment. Based on clinical observation, ammonium chloride was selected for its possible beneficial effect on HCV liver infection due to the intrinsic properties of the compound and its capability to inhibit HCV endosomal pathway penetration in hepatic cells. The aim of the study was to obtain preliminary data on long term ammonium chloride effect on liver function parameters and HCV replication in patients receiving ammonium chloride or placebo both added to the standard of care therapy (peginterferon and ribavirin) for three months followed by three months of standard of care therapy alone (peginterferon and ribavirin; washout from ammoniumchloride or placebo).
Three months after washout from supplementary treatment with ammonium chloride or placebo (administered at the dose regimen of 1.5 g b.i.d. for 3 days a week in addition to standard of care HCV therapy) and after additional three months of standard of care HCV therapy alone, the efficacy of ammonium chloride administration on liver function biochemical parameters (ALT and AST) normalization rate and on virologic (HCV RNA) negativization rate is consistent, statistically significant versus patients receiving placebo and improves within time (p=0.0473, p=0.0094, p=0.0034 for ALT, AST and HCV RNA respectively), while in the placebo group the liver function biochemical parameters (ALT and AST) normalization rate decreases within time as well as the virologic (HCV RNA) negativization rate. Results obtained suggest that ammonium chloride administration offers a longer lasting and more constant protective effect within time, at liver function level, than placebo, both added to standard of care therapy and that standard of care therapy alone is not capable of maintaining liver function biochemical and virologic parameters’ improvement within time. It seems that ammonium chloride initially exerts its activity inhibiting HCV viral replication, subsequently, probably due to progressive reduction of liver parenchyma inflammation, ameliorating liver functions expressed by ALT and AST level normalization. Further studies are required to confirm the preliminary obtained results.