Infection with hepatitis C virus (HCV), an enveloped virus that belongs to the Flaviviridae family of positive-strand RNA viruses, is a major cause of chronic liver disease. WHO estimated that about 170 million people, (3% of the world's population), are infected with HCV and 3-4 million persons are newly infected each year [1–3].
Prevalence rates vary widely, ranging from 0.15% in Scandinavia to about 15% in Egypt . The overall prevalence in the United States is 1.8%, corresponding to an estimated 3.9 million persons with HCV infection .
About 80% of newly infected patients progress to develop chronic infection. Cirrhosis develops in about 10% to 20% of persons with chronic infection. Liver cancer develops in 1% to 5% of persons with chronic infection over a period of 20-30 years [5, 6].
Apart from its numerous contraindications and severe adverse effects, the current recommended treatment for chronic hepatitis C is not only too costly for most persons in developing countries to afford but also weakly effective .
A meta-analysis showed that only about 17% of patients with chronic hepatitis C obtained a sustained virological response on interferon monotherapy, which was the only recommended treatment until the late 1990 .
The current gold standard therapy is a combination of peg-interferon alfa and ribavirin [8, 9]. Patients with genotype 1 infection have a 42%-51% likelihood of achieving a sustained virological response (SVR) after 48 wk of therapy. For patients with genotype 4 (approximately 90% of patients with hepatitis C in Egypt), the sustained virological response (SVR) rate with 48 weeks of therapy ranges from 50% to 60%. A significant proportion of treated patients thus either fail to respond or relapse following an initial response, and a substantial number of patients are unable to tolerate treatment .
Though around 78%-82% of patients with genotype 2 or 3 infection respond to 24 wk of treatment, those with high viral load are difficult to treat (< 70% responders) .
Generally, non-responders to prior standard bitherapy respond to retreatment in about 13% of the cases and relapsers in 58.5% of the cases .
Therapy requires weekly subcutaneous injections, twice-daily oral dosing and frequent visits, with blood tests. Side effects occur in nearly all patients. As a result, 15%-20% of patients in clinical trials and > 25% in clinical practice discontinue therapy.
Ribavirin does not appear to be effective when used alone. Furthermore, there is no clear evidence as to whether treatment reduces the risk of liver related morbidity or mortality .
An alternative treatment which is less costly, safer and more efficacious is being the search of many research authorities al-over the world.
Many herbal products had been studied and proved to offer some hepatoprotective activity and showed some benefits in the treatment of viral hepatitis, Glycyrrhizin, Silymarin, Curcumin, Schiszandra are examples [14–18].
Spirulina is a blue-green alga (cyanobacterium) that has been consumed as food in many countries since ancient times. It is presently marketed as a food supplement (nutraceutical) due to its high contents of proteins, γ-linolenic acid, vitamins and minerals . Many toxicological studies have proven Spirulina's safety. Spirulina now is listed by the US Food and Drug Administration under the category Generally Recognized as Safe (GRAS) [20–24].
Spirulina and many other Cyanobacteria had been found to exhibit many immune-stimulating and antiviral activities not only in-vitro but also in animals and human volunteers. It had been found to activate macrophages, NK cells, T cells, B cells, and to stimulate the production of antibodies and cytokines. It enhances Interferon gamma (IFN-γ) production in an interleukin12, 18 (IL-12/IL-18)-dependent fashion [25–29].
Many natural substances derived from blue-green algae such as Sulfated homopolysaccharides and Sulfoglycolipids demonstrated monocyte/macrophage activation properties and found to substantially increase mRNA levels of key cytokines like interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) .
Calcium spirulan (Ca-SP), a natural sulfated polysaccharide, isolated from Spirulina platensis had been found to be a potent inhibitor against several enveloped viruses. Ca-SP was shown to target not only viral absorption/penetration stages but also some replication stages of progeny viruses after penetration into cells [31, 32].
Whereas Cyanovirin-N (CV-N)[33–35] and Microvirin (MVN)[36, 37] are two examples of mannose specific lectins isolated from blue green algae. They had been found to potently inactivate diverse strains of HIV and other enveloped viruses in nanomolar concentrations through preventing essential interactions between the virus envelope glycoprotein and target cell receptors [33–35].
At low nanomolar concentrations, CV-N was demonstrated to bind to HCV envelope glycoproteins, to block the interaction between the envelope protein E2 and CD81, a cell surface molecule involved in HCV entry [38, 39].
The availability of Spirulina as an over the counter safe dietary supplement with reasonable costs added to the abovementioned data supporting both antiviral and immune-stimulant activities urged us to conduct this pilot clinical trial to test safety and efficacy of this supplement in patients with chronic hepatitis C.