User:Jinyize Jenny Wang/sandbox

Current medication options The only FDA approved treatment, also the standard of care for Hepatitis C, is standard interferon/peginterferon + ribavirin combination therapy, including interferon-2a + ribavirin, interferon-2b + ribavirin, peginterferon-2a + ribavirin and peginterferon-2b+ ribavirin. With the standard care, more than half of chronic hepatitis C patients achieve a sustained viral response (SVR), while a considerable amount of patients are non-responders. The treatment could reach a much higher SVR ranging 75%~100% for acute hepatitis C patients.[1] Peginterferon has better effectiveness than interferon but very expensive; therefore, interferon is more widely used in developing countries. Interferon/peginterferon + ribavirin combination treatment, especially ribavirin, has high toxicity and causes severe side effects, i.e. headache, fever, severe depression, hemolytic anemia, myalgia, arthralgia, neutropenia, thrombocytopenia, etc. Due to financial reasons and low responses of the standard treatment, many patients use herbal medicine and conventional medicine around the world. Traditional Chinese herbal medicine has been proved effective for many patients, but no systematical data collection or related study has been conducted. Some studies show that rhizomes of the Chinese medicinal herb Rhodiola Kirilowii, blueberry leaves extraction—proanthocyandin, and oyster mushroom extraction—laccase are proficient in inhibiting the HCV replication rate.[4][5][6] Anti-HCV herbs, as nutritional supplements and alternative treatments, become more and more accepted in many countries.

Novel therapies Pharmaceutical companies are working on adding four major types of novel therapies to the standard treatment: enzyme inhibitors, therapeutic vaccines, albuferon, and epoetin alpha. Enzyme inhibitors	Enzyme inhibitors inhibit particular enzymes that are needed in HCV life cycles (Figure 1). Once the enzymes fail to take part in the HCV formation pathway, viral load in a patient could be largely reduced. NS3/4A protease inhibitor targets protease complex NS3/4A which consists of serine protease NS3 and its cofactor NS4A. NS3/4A plays an essential role in HCV virus assembly and maturation. Early clinical trial data have shown that NS3/4A protease inhibitor decreases viral load in both treatment-naïve patients and patients that have not responded to current drug therapies. To date, several NS3/4A protease inhibitors showing promising results from clinical trials may launch to the market soon, e.g. Telaprevir, Boceprevir, etc. NS5B polymerase inhibitors target RNA-dependent polymerase NS5B which is involved in HCV protein translation and synthesis, and is incorporated into the elongating RNA strand as chain terminators. A few NS5B polymerase inhibitors are in active clinical trials, e.g. GS9190, IDX184, R7128, etc. Enzyme inhibitor drugs are associated with high toxicity and cause side effects such as headache, flatulence, diarrhea, frequent urination, dry mouth, fatigue, etc. Enzyme inhibitors may cause the presence of drug-resistant virus. Six drug-resistant mutation hot spots of NS3/4A are V36M/A/L, R155K/T/S/M, A156V/T, T54A, A156T, and V170A; four mutation hot spots of NS5B are S282T, S96T, N142T and C316Y.[2] Therapeutic vaccines	No vaccine is commercially available for HCV currently. Vaccines including epitope vaccines, vector vaccines, recombinant protein vaccines and DNA vaccines have been developed over years, and many are in clinical trials. Previous data from clinical trials shows vaccines have good tolerability, effective induction of T cell response that results in accelerating viral load decline and clearance as well as being safe in healthy volunteers. However, more modifications and incorporating combination with peginterferon + ribavirin therapy are required for the new vaccines. Albuferon	Albuferon, also Albinterferon Alfa-2b, is fused of interferon alpha 1b and human serum albumin—a liver protein. Data suggest that Albuferon is well tolerated and has a longer half-life than peginterferon and relatively safer. Side effects of pulmonary complications were observed in clinical trials, usually mild cough and dyspnea.[3] Epoetin alpha		Epoetin alpha is one of the erythropoiesis stimulating agents in treating anemia; the addition of epoetin alpha is used to reduce anemia symptom in HCV patients which is mainly caused by ribavirin. More than 70% of HCV patients developed anemia during peginterferon + ribavirin therapy. The addition of Epoetin achieved a good control of hemoglobin level for those anemia patients.

Future therapies Several new directions for anti-HCV treatment other than interferon/peginterferon + ribavirin are right now at bench stage or animal tests, including viral neutralizing antibodies and miR-122 therapy. Neutralizing antibody	human monoclonal antibodies (mAbs) have been proved to be able to neutralize genetically diverse HCV and protect human liver-chimeric mice against HCV challenge in many studies. miR-122	miR-122 is a liver-specific microRNA(miRNA) and the most abundant miRNA in the liver for ~70% of the total miRNA population, regulating post-transcriptionally in HCV life cycle. Chemical inhibitors of miR-122 are introduced into chimpanzees, chronically infected with HCV, results a sustained reduction in viral load with no detectable adverse effects on liver physiology, which reveals that inhibition of miR-122 would be a new approach to anti-HCV therapy.