Propagermanium: a nonspecific immune modulator for chronic hepatitis B

Abstract

Although antiviral agents have been adopted for the management of chronic hepatitis B, they have only limited efficacy because of the underlying impaired immune status. Propagermanium, a hydrophilic polymer of 3-oxygermyl propionate, has been reported to have potent immune modulatory activity associated with antiinflammatory and antineoplastic properties. For example, propagermanium augments lymphocyte functions in CD4 and CD8 cells, and in natural killer (NK) cells, and induces the production of several cytokines. A controlled pilot study of 16-week treatment with propagermanium for chronic hepatitis B (of moderate and mild grades on hepatic histology) revealed a sustained clearance of hepatitis B e (HBe) antigen and a favorable biochemical response at week 16 of treatment and at week 48 post-treatment. An open study also supported the clearance of hepatitis B virus from the blood and the possible improvement of histologic grading in the liver. There were few adverse events. A postmarketing survey, however, revealed the occurrence of moderate to severe liver damage after the treatment in about 4% of patients. Despite the exact nature of the liver damage being unclear, a putative cause is the swift removal of virus-infected hepatocytes by an immune reaction through the treatment. A subtle balance between host and viral conditions is the factor which most determines hepatitis B virus persistence. The rationale for a nonspecific immune modulator for the treatment of chronic hepatitis B will be the restoration of cellular immune responsiveness to viral infection. Although the cellular immunity for hepatitis B virus prior to the treatment should be studied, adequate observation of hepatic functions and viral markers in the recipients is clinically useful to predict liver failure during the treatment. In summary, the propagermanium regimen offers a potent and safe approach that is cost-effective for appropriate chronic hepatitis B patients with reserve hepatic capacity, and will provide new perspectives for immune therapy in chronic hepatitis B.

C-C Chemokine Receptor 2 Inhibitor Improves Diet-Induced Development of Insulin Resistance and Hepatic Steatosis in Mice

“…Propagermanium has been used as a therapeutic agent against hepatitis B virus-induced chronic hepatitis in Japan 22) . Recently, Yokochi et al demonstrated that this drug suppressed monocyte migration in vitro and macrophage infiltration in vivo by inhibiting CCR2 function.…”

Metabolism of tellurium, antimony and germanium simultaneously administered to rats

“…In addition, an Sb compound was developed as an antitumor agent (Sharma et al, 2008). A Ge-containing drug, propagermanium, was evaluated for potential use as an immunomodulator (Hirayama et al, 2003). As mentioned above, as the risk of exposure to Te, Sb and Ge is expected to increase, the toxicological effects of these metalloids should be fully understood.…”

The CCR2 inhibitor propagermanium attenuates diet-induced insulin resistance, adipose tissue inflammation and nonalcoholic steatohepatitis

“…The late intervention group received HFD supplemented with propagermanium from 12 weeks onwards for another 12 weeks (HFD+Pro_12w). Propagermanium is an organic compound, which has been clinically used for the treatment of hepatitis B virus-induced chronic hepatitis [18]. The current concentration of propagermanium has been previously used [16] and did not show adverse effects.…”