Safety and efficacy of alamifovir in patients with chronic hepatitis B virus infection

Soon, Danny; Lowe, Stephen L.; Teng, Choo Hua; Yeo, Kwee Poo; McGill, James M.; Wise, Stephen D.

doi:10.1016/j.jhep.2004.07.028

Cited by 11 publications

(6 citation statements)

References 19 publications

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“…The biochemical markers AST, ALT, TP, ALB and LDH are widely used to diagnose many types of human hepatitis [ 26 , 36 , 37 ]. These markers are of great significance in differential diagnoses, curative effect monitoring and evaluations of hepatitis.…”

Section: Discussionmentioning

confidence: 99%

Assessment of a Flavone-Polysaccharide Based Prescription for Treating Duck Virus Hepatitis

et al. 2016

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Because polysaccharide and flavone ingredients display good antiviral activity, we developed a flavone/polysaccharide-containing prescription that would be effective against duck viral hepatitis (DVH) and investigated its hepatoprotective effects. Flavones were derived from Hypericum japonicum (HJF) (entire herb of Hypericum japonicum Thunb) and Salvia plebeia (SPF) (entire herb of Salvia plebeia R. Br.), and polysaccharides were derived from Radix Rehmanniae Recens (RRRP) (dried root of Rehmannia glutinosa Libosch). This prescription combination was based on the theory of syndrome differentiation and treatment in traditional Chinese veterinary medicine. In vitro and in vivo experiments were conducted using the three single ingredients compared to the combined HRS prescription to determine their anti-duck hepatitis A viral (anti-DHAV) activity. The results showed that all experimental conditions displayed anti-DHAV activity, but the HRS prescription presented the best effect. To further investigate the hepatoprotective effect of the HRS prescription on DHAV-induced hepatic injury, we tested the mortality rate, the hepatic pathological severity score, plasma biochemical indexes of hepatic function, blood DHAV gene expression levels and peroxidation damage evaluation indexes and then analyzed correlations among these indexes. The results demonstrated that the HRS prescription significantly decreased the mortality rate, reduced the severity of hepatic injury, decreased the hepatic pathological severity score, depressed blood DHAV gene expression levels, and returned the indexes of hepatic function and peroxidation almost to a normal level. These results indicate that the HRS prescription confers an outstanding hepatoprotective effect, and we expect that it will be developed into a new candidate anti-DHAV drug.

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Section: Discussionmentioning

confidence: 99%

Assessment of a Flavone-Polysaccharide Based Prescription for Treating Duck Virus Hepatitis

et al. 2016

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“…MCC-478, an adefovir derivative, has been in clinical Phase I trials for safety and efficacy assessment [ 43 , 44 ]. It acts similarly to other NAs and can inhibit HBV replication by inhibiting P protein packaging reaction.…”

Section: New Anti-hbv Drugs Under Development and Evaluationmentioning

confidence: 99%

Anti-HBV Drugs: Progress, Unmet Needs, and New Hope

Liu

Pan

et al. 2015

Viruses

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Approximately 240 million people worldwide are chronically infected with hepatitis B virus (HBV), which represents a significant challenge to public health. The current goal in treating chronic HBV infection is to block progression of HBV-related liver injury and inflammation to end-stage liver diseases, including cirrhosis and hepatocellular carcinoma, because we are unable to eliminate chronic HBV infection. Available therapies for chronic HBV infection mainly include nucleos/tide analogues (NAs), non-NAs, and immunomodulatory agents. However, none of them is able to clear chronic HBV infection. Thus, a new generation of anti-HBV drugs is urgently needed. Progress has been made in the development and testing of new therapeutics against chronic HBV infection. This review aims to summarize the state of the art in new HBV drug research and development and to forecast research and development trends and directions in the near future.

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“…Furthermore, introduction of the arylthio group at position 6 of the 2-aminopurine base has been demonstrated to endow the purine base with a higher selectivity against HBV and lower cytotoxicity comparable to that of PMEA (Chan et al, 2005;Quan and Peters, 2004;Wang et al, 2005). Apparently, substitution at position 6 of the purine base may alter the biological and toxicological profiles of the phosphonomethoxyethyl purine derivatives Sekiya et al, 2002;Soon et al, 2004). We propose that those novel compounds may be metabolized in vivo, mediating the anti-HBV activity.…”

Section: Discussionmentioning

confidence: 80%

Antiviral effects of three novel derivatives of adefovir on the replication of hepatitis B virus

Niu

Ding

et al. 2011

Med Chem Res

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Nucleoside/tide analogs are now widely used for treatment of chronic hepatitis B (CHB). However, available nucleoside/tide analogs for treatment of CHB usually have limited therapeutic effect and potential adverse effects on CHB patients. We evaluated the anti-HBV effects of three novel derivatives (compounds 1, 4, and 8) of adefovir on the replication of hepatitis B virus (HBV) and determined their cytotoxicity. The effects of those compounds on the replication of human HBV in the HepG2 2.2.15 cell line and duck HBV in infected ducks were characterized by measuring the extracellular and intracellular HBV DNA using the quantitative real-time PCR and Southern blot assays. Their cytotoxicities against HepG2 cells were evaluated by MTT and measuring the contents of mitochondrial DNA using the dot blot assay. We found that all of the compounds inhibited the production of HBV in a dose-dependent manner, similar to that of adefovir dipivoxil. Furthermore, treatment with any of the compounds reduced significantly the replication of DHBV in ducks, accompanied by a significant reduction of inflammation in the livers, and the compound 1 appeared to be a fast-acting and long-lasting anti-DHBV reagent. Importantly, all of the compounds showed little cytotoxicity against HepG2 cells, even at a concentration of 1 mM. Collectively, those novel derivatives of adefovir had potent anti-HBV activity with little adverse effect and may be therapeutic candidates for potential clinical studies.

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Safety and efficacy of alamifovir in patients with chronic hepatitis B virus infection

Cited by 11 publications

References 19 publications

Assessment of a Flavone-Polysaccharide Based Prescription for Treating Duck Virus Hepatitis

Assessment of a Flavone-Polysaccharide Based Prescription for Treating Duck Virus Hepatitis

Anti-HBV Drugs: Progress, Unmet Needs, and New Hope

Antiviral effects of three novel derivatives of adefovir on the replication of hepatitis B virus

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