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3.3.0 Treatment strategies

3.3.0 Treatment strategies

So what can you do if you can’t get rid of the virus? Watch your weight. Control any diabetes. Don’t drink or smoke. Drink coffee, but in moderation. If you can’t wait for the newer treatments, consider 72-week therapy. (EASL Conference 2009)

Below are some more possibilities.

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3.3.1 Dosage

3.3.1a Mega Dosing

A study of patients with normal ALTs concluded that these patients should be treated with high doses of IFN
if they show a favorable response (Hepatogastroenterology. 2003 Jan-Feb;50(49):165-9).

There have been many studies, mostly in non-responders, with high doses of interferon, either at the beginning of therapy (induction doses) or during therapy itself. The side effects are greater, and more people drop out of these trials. Studies are being done with consensus interferon in high doses (www.natap.org High Dose Censensus Interferon in Peg-IFN/Ribavirin Nonresponders, Reported by Jules Levin, May 2003.), in various doses (www.natap.org High Dose Censensus Interferon in Peg-IFN/Ribavirin) and a Phase III clinical trial tested daily injection of consensus interferon taken with Ribavirin.
(www.hcvadvocate.org  See 3.2.3a)

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3.3.1b Maintenance Dosing

A low-dose maintenance trial was done in Germany with 182 non-responders with significant liver scarring, who were compared to a control group who received no treatment. The patients were given peg-IFN alpha-2b at a dose of 0.5 ug/kg once a week for 36 months. An increase in the fibrosis score from 3.71 to 4.79 at 6 months post-therapy was detectable in the control group. In the treatment group, a decrease from 3.83 at baseline to 2.05 at 6 months post-therapy was observed. Inflammation decreased during treatment, but returned to baseline levels when treatment ceased. Treatment was well tolerated. These researchers believe that this may be a good “salvage” therapy for non-responders.
(AASLD, Boston, MA, Nov 2-6, 2007 www.natap.org/2007/AASLD/AASLD19.htm)

“The HALT-C trial demonstrated that prolonged low-dose PEG IFN therapy can not reduce the occurrence of clinical outcomes in a large population of patients with non-cirrhotic fibrosis or cirrhosis who had an initial non-response to antiviral standard therapy.”

The large EPIC maintenance trial with low-dose pegIFN alpha-2b in cirrhotic non-responders to standard therapy concluded that long-term, low-dose therapy with pegIFN alpha-2b does not prevent HCC (hepatocellular carcinoma or liver cancer) in cirrhotics. It may, however, be beneficial for those with cirrhosis and portal hypertension. (EASL Conference 2009)

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3.3.1c Induction Dosing

Induction dosing involves giving higher or more frequent doses of interferon for a period before regular
dosing commences.

One study has shown that induction dosing with consensus interferon does not improve SVR.

At the AASLD Annual Meeting in Dallas, Texas, in October 2000, it was shown that a high daily dose of IFN alpha has no significant effect on the long-term results if the treatment schedule is changed to a 3-times-weekly regimen later on during therapy.

Induction doses are now being tested with the pegylated interferons and ribavirin. The REPEAT study (See 3.3.3 below) showed that induction with pegylated Pegasys with Copegus did not help previous non-responders.

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3.3.2 Early Treatment

HCV patients who are treated within a few months of being infected usually have a fast immune response, which helps eradicate the virus, according to Canadian research study published in the Journal of Virology. Only about 25% of patients get rid of the virus without treatment. Treatment is usually only effective in about 50% of cases, but those treated early have a 90% or more chance of getting rid of the virus. The research studied a group of IVDU before and after they were exposed to HCV. The results show how important it is to diagnose the disease quickly.
(www.upi.com Aug. 12, 2008)

Patients with little or no fibrosis (scarring) respond better to standard treatment than those with advanced fibrosis. Since response rates are higher in patients with little liver damage, early treatment has better success. For patients with stage 0-2 cirrhosis, there may be an advantage by using high (induction) dose before starting standard therapy. Poor drug metabolism in the liver may explain worse response among cirrhotics. (EASL Conference 2009)

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3.3.3 Longer Treatment

Roche’s REPEAT study of 950 non-responder patients showed that 72 weeks of Pegasys with Copegus is a promising option, and a viral response at 12 weeks usually predicts whether or not a patient will achieve a sustained virological response (SVR). All patients took Copegus (ribavirin). SVR was achieved in 16% of patients taking 360 mcg/week of Pegasys for 12 weeks (high dose induction therapy), followed by 180 mcg/week (standard therapy) for 60 weeks. 9% of patients receiving 180 mcg/week of Pegasys for 48 weeks achieved SVR. High dose induction therapy did not help. Longer dosing did help patients with a viral response at 12 weeks, with 57% of those patients achieving SVR. Relapsers were not included in this trial. They are easier to treat than non-responder patients.
( www.rocheusa.com November 2, 2007)

A study presented at the EASL Conference 2009, proposed that patients with RVR (undetectable virus at 4 weeks) should have 24 weeks of treatment; patients without RVR but with EVR (more than 2-log drop in viral load and/or a viral load less than 50 IU/mL at week 12) should be treated for 48 weeks; patients with EVR but with a week-12 viral load of more that 50 IU/mL should continue for 72 weeks; patients who don’t have EVR should not receive further treatment. Their chance of responding is less than 5%. Patients with EVR with still detectable virus had a 77% SVR rate when treated for 72 weeks compared to 37% of those treated for 48 weeks.

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3.3.4 Retreatment

"57% of patients with undetectable HCV RNA at week 12 achieved an SVR in the extended treatment arms. This suggests that it is possible to identify patients most likely to achieve an SVR before treatment."

The factors indicating treatment success included a viral load less than 800,000 IU/ml, age under 45 years,
body weight under 75 kg, no cirrhosis, and a genotype other than 1.

About 65% of previous non-responders with these characteristics and a viral response at week 12 were able to achieve an SVR (sustained viral response or “cure”) after 72 weeks of treatment, rather than the usual 48 weeks. (EASL Conference 2009)

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3.4.0 Iron Reduction Therapy

The idea that iron reduction, through diet or blood letting, could help improve response to standard treatment was explored in the recent past. That it has not been widely adopted may be an indication of its effectiveness.

Iron is required for replication of virtually all virulent micro-organisms. The role of iron influencing the natural history of viral hepatitis was reported in a study more than 15 years ago (Blumberg BS, Lustbader ED, Whitford PL.

“Changes in serum iron levels due to infection with hepatitis B virus.” Proc Natl Acad Sci USA 1981;78:3222-4). In this study it was observed that patients with hepatitis B viral infection with higher serum iron or ferritin levels had greater likelihood of development of chronic infections than those with lower levels, who more often resolved their infections spontaneously.

Complete responders to interferon have, on average, lower hepatic iron concentrations than do non-complete responders. Hepatic iron concentration as a predictor of response to interferon alpha therapy in chronic hepatitis C.

Studies done since 1998 showed that phlebotomy (bloodletting), combined with IFN, reduces liver inflammation but not fibrosis. It seems to reduce the viral load, and may improve sustained response, but the results are not enough to be statistically important (Journal of Hepatology 1998; 28:369-374 and Hepatology 2000; 31:730-736). These studies were not done combining the interferon with ribavirin. Ribavirin tends to result in anemia.

Tandon et al. (Br. J. Nutr. 1999) have shown that a special low-iron vegetarian diet was able to significantly reduce the serum iron and ferritin levels. Kimura F, et al. agree with a low-iron diet to enhance phlebotomy. (Hepatogastroenterology. 2005 Mar-Apr;52(62):563-6, but a more recent study (2007) showed that phlebotomy is better than diet for reducing liver damage.

Phlebotomy alone does not completely remove iron-induced oxidative stress, but a low iron diet induces an additional effect in iron reduction therapy for chronic hepatitis C. (Hepatogastroenterology. 2005 Mar-Apr;52(62):563-6)

Iron reduction improved the serum levels of aminotransferases and α-fetoprotein in Hep C patients with liver cirrhosis and was generally safe; however, it should be used only in patients who maintain serum albumin concentrations of more than 3.6 g/dL. (Journal of Gastroenterology, Volume 42, Number 1, January 2007 , pp. 49-55)

Bovine lactoferrin, 1.8–3.6 g/day for 8 weeks, suppressed ALT levels and viral load in 3 of 11 patients. This could be used with any combination of antiviral therapies, including IFN plus ribavirin, without side effects (Jpn. J. Cancer Res. 1999; 90: 367– 71).

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Table of Contents


3.2.3l Oral Interferon

Hepatitis C FAQ

Part 4: Research