Get your own Free Home PageIRON REDUCTION THERAPY
A new study published in the fall issue of American Journal of Gastroenterology, Vol 89, No. 7, suggests that using "Iron Reduction Therapy" along with interferon can result in an effective cure rate in the area of 75-80% and that adding cytokines and antivirals such as ribavirin can improve effectiveness even further. The theory behind this is that viruses need iron to replicate, and by reducing the hepatic iron in the liver you prevent them from replicating. It should be noted that this new procedure is not yet FDA approved and is still in the early trial stages.
Iron is an element required for replication of virtually all virulent microorganisms. Reducing the amount of iron helps to limit the replication of the hepatitis C virus. 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.
Increases in levels of serum ferritin, iron, and transferrin saturation also have been noted with high frequencies in patients with chronic hepatitis C, and the higher levels have, in general, been associated with lesser likelihood of response to interferon therapy. Complete responders to interferon have, on average, lower hepatic iron concentrations than do noncomplete responders.
In a report by Hayashi and colleagues ("Improvement of serum aminotransferase levels after phlebotomy in patients with chronic active hepatitis C and excess hepatic iron." Am J Gastroenterol 1994;89:986-8) it was reported that iron reduction alone, by repeated venesection (bloodletting), led to significant improvement in serum alanine aminotransferase (ALT) levels in chronic hepatitis C.
GENDER / IRON RELATIONSHIP - The median estimated duration of infection for progression to cirrhosis was 30 years (28-32), ranging from 13 years in MEN infected after the age of 40, to 42 years in WOMEN who did not drink alcohol and were infected before the age of 40( is it maybe because of women's regular period phlebotomy ? )
LONG-TERM EFFECT OF IRON REMOVAL ON CHRONIC HEPATITIS C
H Hayashi, S Wakusawa, T Takikawa, N Arai, M Yano*, S Kato{**},
M Arao{**} Dept. of Med., Hokuriku Univ., *Third Dept. of Int.
Med., Nagoya Univ. and {**}Dept. of Med., Inazawa City Hospital,
Japan; Source: American Association for the Study of Liver Diseases
- 1996 Annual Meeting
Phlebotomy with a 10 ng/ml end point for the serum ferritin level reduces liver enzymes in patients with chronic hepatitis C (CHC). Here we report the long-term effects of iron removal on patients, including histological changes and complication by hepatocellular carcinoma. Thirty patients who had reached the end point of inital phlebotomy were followed for more than 3 years and given maintenance phlebotomy, if needed, to maintain the iron depleted state. Ursodeoxycholic acid or azathioprine was permitted with our dosage change throughout the study period. Twenty-three patients received non-effective interferon treatment within a year after reaching the end point.
Initial phlebotomy significantly reduced serum levels of ALT and maintenance phlebotomy stablized the improved liver function test for the study period (Table). There was no effect on circulating HCV RNA.
..............................ALT (U/l)...hemoglobin(g/dl)...ferritin(ng/ml)
pretreatment(n=30)...124±68......14.0±1.4........204±180
posttreatment(n=30)...76±38......11.4±1.4............8±2
3 years(n=30)............67±33......11.8±1.5...........15±15
4 years(n=11)............58±27......12.4±1.9...........11±5
Serum ALT levels 3 and 4 years posttreatment remained significantly
lower than the pretreatment level.
Histology of biopsied livers remained the same in 4 patients and progressed in one patient from CAH 2A to 2B. Hepatocellular carcinomas, all less than 20 mm in diameter, developed in 5 patients. Two patients were successfully treated by hepatectomy, 3 by transarterial embolization. None of the patients died during the study period.
These data indicate that iron removal from CHC patients is effective for at least 4 years, if combined with maintenance phlebotomy. Long-term biochemical improvement may be associated with a slower progression in liver histology. The effect of iron removal on malignant change should be further investigated, since iron deficiency is considered unfavorable for malignant growth.
RETREATMENT OF HEPATITIS C INTERFERON NONRESPONDERS WITH LARGER DOSES OF INTERFERON WITH AND WITHOUT PHLEBOTOMY
Vanthiel Dh, Univ Kentucky, Transplant Ctr, 800 Rose St, Lexington, Ky 40536; Hepato-Gastroenterology 1996 Nov-Dec;43(12):1557-1561
Background/Aims: Interferon a (IFN) is the only agent currently approved by the FDA for the treatment of chronic viral hepatitis due to hepatitis C (HCV). Unfortunately, less than half the patients with HCV treated with IFN respond. Worse yet, half or more of those who do respond relapse when the agent is withdrawn.
Materials and Methods: In this prospective randomized study, 30 individuals who had failed to respond to a standard course of IFN therapy consisting of 3 MU IFN administered 3 x week for 6 months were randomized to receive a second 6 month course of either 5 MU IFN daily or 5 MU IFN plus regular phlebotomies at weekly intervals to achieve a hemoglobin level of between 10-11 g/dl. The response rates defined as HCV-RNA negativity after 6 months of therapy and after 6 months of follow-up without IFN were determined.
Results: Both groups experienced a significant reduction in their serum ALT levels (p <0.01) and Knodell scores with treatment. A greater number of responders were found in the phlebotomy plus IFN group than in the IFN alone group whether the response was defined by the serum ALT level or presence or absence of HCV-RNA in serum at the end of treatment and follow-up.
Conclusions: The results of this study suggest that both an increased IFN dose coupled with more frequent dosing of IFN alone and combined with phlebotomy treatment are effective at obtaining a response to IFN in individuals with HCV disease who previously have failed to respond to a standard treatment regimen.
RIBAVIRIN INTERFERON COMBINATION WITH PHLEBOTOMY
Y. Lurie,?(1) M. Beer-Gabel,(1) S.D.H. Malnick,(2) I. Lambort,(1) T. Soumatzki,(1) A. Kaftory,(3) A. Fink,(3) D. Ketter,(1) M. Cooper,(4)M. Illuz,(1) Y. Bass Elhanany, (5) D.D. Bass,(1) 1. Institute of gastroenterology 2. Dept. of medicine "C" 3. Division of laboratories 4, Pediatric Day-care 5. Pharmacy, Kaplan Hospital Rehovot, Israel. From: American Gastroenterology Association Digestive Disease Week meeting in Washington in May 1997.
Background : Alpha interferon is currently the only licensed drug for Chronic Hepatitis C (=CHC). As monotherapy it is unsatisfactory. Recent data from several countries suggest that Ribavirin interferon combination (=Ribinf) is an important improvement. There are also indications that phlebotomy is beneficial in CHC.
Aim to evaluate Ribinf in CHC patients who were either relapsers or non responders to previous interferon therapy. Methods We undertook a 1 year open trial of Ribinf (interferon alpha 2b 9MU/WK plus Ribavirin 1000 mg/dy for wt<75Kg, 1200 mg/dy for wt>75Kg) in 21 selected CHC patients. Patients also underwent phlebotomy, mostly prior to Ribinf, aiming at serum ferritin of 10 ng/ml.
Patient's characteristics: Mean age: 48 ± 13 (range 16 to 68), 13 women, genotypes: 1b-18, 3a-2 ND-1. Relapsers/non responders: 8/13 Histology:CIR-3, CPH-2, CAH-5, CAH+Fib-9, ND2
Results Alt levels declined into normal range in 20/21 patients. As shown in the figure, Mean levels for the group (expressed as multiples of the upper limit of normal values.) and 9 out of 16 patients tested, became serum HCV RNA negative.
The combination had few side effects and was well tolerated. Hemoglobin dropped approximately 2 g/dl. The lowest hemoglobin value recorded in the group was 9 g/dl. One patient developed thyrotoxicosis and continues treatment. There were two dropouts - a patient who developed depression, and one for unrelated causes.
Conclusions: Ribinf (with prior phlebotomy) yielded a 95% biochemical response rate in less than 120 days. Our patients were predominantly non responders to previous INF therapy with the unfavorable genotype 1b. These results are markedly better than the widely quoted approximately 50% biochemical response rate at the end of INF treatment. Ribinf and phlebotomy either alone or with other modalities, are an important addition to our therapeutic armamentarium.
THRESHOLD EFFECT OF LIVER IRON CONTENT ON HEPATIC INFLAMMATION
AND FIBROSIS IN HEPATITIS B AND C
Nele K. Beinker, Michael D. Voigt, Michael Arendse, Julian Smit, Ilse A. Stander and Ralph E. Kirsch , J of Hepatology 1996, vol 25 issue 5( November )
Background/Aims: In hepatitis C, iron depletion may improve serum aminotransferases and the response to interferon, but it is not known whether inflammation and fibrosis correlate with hepatic iron content. Our aim was to establish whether hepatic iron content correlates with histological and serum indices of hepatic inflammation and fibrosis in hepatitis B and C. Methods: Total hepatic iron was measured using computerized histomorphometry, and hepatic inflammation and fibrosis using a modified Knodell score, on histological slides from 31 patients with chronic hepatitis B and 38 with hepatitis C.
Results: Total hepatic iron was similar in the hepatitis B and C groups (0.82±1.72% and 0.56±1.12%; mean±SD). No iron was detectable in 11 patients with hepatitis B and 13 with hepatitis C. Alanine aminotransferase (85.96±67.1 vs 44.2±39.7 p<0.05), aspartate aminotransferase (93.8±75.6 vs 47±33.5 IU/ml p<0.05) and histological inflammatory score (9.33±3.51 vs 7.79±3.3 p=0.07) were increased in those with stainable hepatic iron compared to those without. However, where iron was present, no association was found between the amount of hepatic iron and inflammatory or fibrosis scores. In hepatitis C, fibrosis was minimal in 77% of patients if iron was absent vs 24% with iron present, while marked fibrosis was present in 56% with iron vs 15% without iron (p<0.01, Fisher’s exact test).
Conclusion: Hepatic iron is associated with increased hepatic
inflammation in chronic hepatitis B and hepatitis C and with high
fibrosis scores in hepatitis C. There is a threshold effect, and
once present, increasing iron does not correlate with increasing
inflammation or fibrosis.
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