Therapy of hepatitis C: Other options

Abstract

Because current standard therapy of chronic hepatitis C ultimate therapeutic goal continues to be eradication of all detectable virus in the blood, liver, or other organs. However, with alpha interferon is less than ideal, numerous other approaches have been studied. Iron in the liver, particularly that because of the ability of hepatitis C virus (HCV) to mutate rapidly and become resistant to antiviral agents and immune found in vascular endothelial cells of portal tracts, has been associated with decreased responsiveness to alpha interferon surveillance, the value of achieving other, lesser therapeutic goals should not be minimized. Such goals might include therapy. Iron reduction alone, generally achieved by therapeutic phlebotomy, regularly has been associated with biochemi-the following: (1) diminution of levels of virus in the blood and risk of infectivity; (2) diminution in the severity of hecal improvement (decrease in serum alanine aminotransferase), but not with virological improvement. Iron reduction patic inflammation and necrosis; (3) diminution in the rate of progression of hepatic fibrosis and development of cirrhohas been reported to increase the therapeutic response to alpha interferon. Most studies of this combination have been sis; and (4) prevention or delay in development of complications of cirrhosis, particularly hepatocellular carcinoma. conducted in patients who had not responded to interferon alone; in these patients, improved responsiveness has beenThe eventual conquest of HCV infection will depend on development of an effective vaccine. Even when that goal observed in some, but not all studies. In patients not previously treated, iron reduction was found in a recent trial to has been reached, many patients will remain who are already chronically infected with the virus. Accordingly, approaches improve the sustained biochemical and virological response rate from 5% to 29%. Hepatic iron and chronic hepatitis C to management of chronic hepatitis C, beyond the use of interferons, with or without ribavirin, are worthy of considerincrease oxidative stress in the liver and are associated with decreases in hepatic glutathione levels. In one report, adminis-ation. This review summarizes the current status of other approaches to therapy of chronic hepatitis C (Table 1). tration of N-acetyl cysteine, a sulfhydryl donor, led to improved response to interferon in chronic hepatitis C. Several IRON REDUCTION cytokines and immunomodulators have undergone limited study; perhaps the most promising of these is thymosin a-1. Role of Iron in Infectious DiseasesIn one small study, amantadine was found to produce some It has been recognized for many years that iron is an eleresponse in patients who previously had failed to respond to ment essential to the replication of virtually all organisms, interferon. Ursodiol improves serum aminotransferase levels including virulent microorganisms. Many clinical observain chronic hepatitis C but has no antiviral effect, nor has it tions and experimental studies have e...

A significant reduction in serum alanine aminotransferase levels after 3-month iron reduction therapy for chronic hepatitis C: a multicenter, prospective, randomized, controlled trial in Japan

“…Therefore, when a patient is found to have an active form of CHC, iron reduction therapy should be recommended as an alternative to antiviral agents. 33 Once iron reduction therapy for CHC is authorized in Japan, great benefit might be provided for patients who need adjuvant therapy other than IFN.…”

Iron Cytotoxicity in Chronic Hepatitis C.

“…26,27) In Europe and the United States, individuals with C282Y mutation are so common that ironinduced oxidative stress and its prophylaxis are major issues even in patients with CHC. Bonkovsky, in a review of other options to IFN in CHC, 5) recommended iron reduction therapy as the first line among various regimens including ursodeoxhycholic acid and herbal medicines.…”

“…tients fail to respond to these treatments and require additional treatment. 5) The therapeutic effects of iron reduction therapy on CHC, 6,7) which we first empirically introduced based on lysosomal iron stores detected under an Xray microanalyzer, 8) suggested that most patients are exposed to iron-induced oxidative stress. This is particularly important for male patients with a positive balance of iron.…”

Estimate the Levels of Copper in Serum Samples of Hepatitis C Patients at Different Stages after Interferon-α Therapy

“…Exposure to high levels of Cu results in various changes in the liver tissues that are consistent with oxidative damage to membranes and molecules. Lipid peroxidation causes dysfunction in the cell membrane, decreased fluidity, inactivation of enzymes and changes ion permeability [10,11]. Hatano studied that Cu accumulation in fibrotic livers caused by chronic hepatitis C may contribute to hepatic injury [12].…”