Advertisement

Journal of Gastroenterology

, Volume 44, Issue 6, pp 577–582 | Cite as

Efficacy and safety of addition of minor bloodletting (petit phlebotomy) in hepatitis C virus-infected patients receiving regular glycyrrhizin injections

  • Naoki Tanaka
  • Akira Horiuchi
  • Takahiro Yamaura
  • Michiharu Komatsu
  • Takahide Yokoyama
  • Shinji Okaniwa
  • Tadanobu Nagaya
  • Kaname Yoshizawa
  • Kendo Kiyosawa
  • Toshifumi Aoyama
  • Eiji Tanaka
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

Hepatoprotective therapies that include regular glycyrrhizin injections (GIs) are beneficial for chronic hepatitis C patients, but are sometimes insufficient for normalizing serum alanine aminotransferase (ALT) levels. Here, we evaluated whether the addition of minor bloodletting, named petit phlebotomy (PP), prior to each GI could further reduce serum ALT concentrations in such patients.

Methods

Seventy-six hepatitis C virus (HCV)-infected patients receiving regular GI, with persistently abnormal serum ALT levels, were randomly divided into GI + PP and GI groups and monitored for 12 months. PP was performed before every GI to a total 60 ml of blood a week. The primary PP endpoint was a serum ferritin level of less than 20 ng/ml. PP was suspended upon reaching the endpoint, but was resumed as needed. The efficacy of the addition of PP was evaluated by measuring changes in serum ALT levels.

Results

Two patients in each group dropped out because of the appearance of hepatocellular carcinoma. The remainder completed the 12-month treatment with no serious adverse events. Serum ALT and ferritin levels were significantly decreased in the GI + PP group (from 67 ± 34 to 44 ± 14 U/l and from 163 ± 127 to 25 ± 21 ng/ml, respectively, both P < 0.001), but these changes were not seen in the GI group. Although 20 patients in the GI + PP group had compensated cirrhosis, no significant reductions in serum albumin concentrations were observed.

Conclusions

The addition of PP is effective and safe for improving serum aminotransferase levels in HCV-infected patients receiving regular GI, even in those with compensated cirrhosis.

Keywords

Petit phlebotomy Hepatitis C Liver cirrhosis Glycyrrhizin injection Ferritin Albumin 

Notes

Acknowledgments

We thank the nursing, nutrition, and laboratory staff for their skilled work and Mr. Trevor Ralph for his editorial assistance.

References

  1. 1.
    Kiyosawa K, Sodeyama T, Tanaka E, Gibo Y, Yoshizawa K, Nakano Y, et al. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology. 1990;12:671–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Tarao K, Rino Y, Ohkawa S, Endo O, Miyakawa K, Tamai S, et al. Sustained low alanine aminotransferase levels can predict the survival for 10 years without hepatocellular carcinoma development in patients with hepatitis C virus-associated liver cirrhosis of Child stage A. Intervirology. 2004;47:65–71.PubMedCrossRefGoogle Scholar
  3. 3.
    Tanaka N, Kiyosawa K. Phlebotomy: a promising treatment for chronic hepatitis C. J Gastroenterol. 2004;39:601–3.PubMedGoogle Scholar
  4. 4.
    Kaito M. Molecular mechanism of iron metabolism and overload in chronic hepatitis C. J Gastroenterol. 2007;42:96–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Hayashi H, Takikawa T, Nishimura N, Yano M, Isomura T, Sakamoto N. 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.PubMedGoogle Scholar
  6. 6.
    Yano M, Hayashi H, Yoshioka K, Kohgo Y, Saito H, Niitsu Y, et al. 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. J Gastroenterol. 2004;39:570–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Tanaka N, Horiuchi A, Yamaura T, Komatsu M, Tanaka E, Kiyosawa K. Efficacy and safety of 6-month iron reduction therapy in patients with hepatitis C virus-related cirrhosis: a pilot study. J Gastroenterol. 2007;42:49–55.PubMedCrossRefGoogle Scholar
  8. 8.
    Tanaka N, Tanaka E, Sheena Y, Komatsu M, Okiyama W, Misawa N, et al. Useful parameters for distinguishing nonalcoholic steatohepatitis with mild steatosis from cryptogenic chronic hepatitis in the Japanese population. Liver Int. 2006;26:956–63.PubMedCrossRefGoogle Scholar
  9. 9.
    Tanaka N, Sano K, Horiuchi A, Tanaka E, Kiyosawa K, Aoyama T. Highly purified eicosapentaenoic acid treatment improves nonalcoholic steatohepatitis. J Clin Gastroenterol. 2008;42:413–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Tanaka N, Nagaya T, Komatsu M, Horiuchi A, Tsuruta G, Shirakawa H, et al. Insulin resistance and hepatitis C virus: a case-control study of non-obese, non-alcoholic and non-steatotic hepatitis virus carriers with persistently normal serum aminotransferase. Liver Int. 2008;28:1104–11.PubMedGoogle Scholar
  11. 11.
    Ikeda K, Saitoh S, Kobayashi M, Suzuki Y, Tsubota A, Suzuki F, et al. Distinction between chronic hepatitis and liver cirrhosis in patients with hepatitis C virus infection: practical discriminant function using common laboratory data. Hepatol Res. 2000;18:252–66.PubMedCrossRefGoogle Scholar
  12. 12.
    Ikeda K, Arase Y, Kobayashi M, Saitoh S, Someya T, Hosaka T, et al. A long-term glycyrrhizin injection therapy reduces hepatocellular carcinogenesis rate in patients with interferon-resistant active chronic hepatitis C: a cohort study of 1249 patients. Dig Dis Sci. 2006;51:603–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Kato J, Kobune M, Nakamura T, Kuroiwa G, Takada K, Takimoto R, et al. Normalization of elevated hepatic 8-hydroxy-2′-deoxyguanosine levels in chronic hepatitis C patients by phlebotomy and low iron diet. Cancer Res. 2001;61:8697–702.PubMedGoogle Scholar
  14. 14.
    Kato J, Miyanishi K, Kobune M, Nakamura T, Takada K, Takimoto R, et al. Long-term phlebotomy with low-iron diet therapy lowers risk of development of hepatocellular carcinoma from chronic hepatitis C. J Gastroenterol. 2007;42:830–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2009

Authors and Affiliations

  • Naoki Tanaka
    • 1
    • 2
  • Akira Horiuchi
    • 3
  • Takahiro Yamaura
    • 4
  • Michiharu Komatsu
    • 2
  • Takahide Yokoyama
    • 5
  • Shinji Okaniwa
    • 4
  • Tadanobu Nagaya
    • 2
  • Kaname Yoshizawa
    • 2
  • Kendo Kiyosawa
    • 6
  • Toshifumi Aoyama
    • 1
  • Eiji Tanaka
    • 2
  1. 1.Department of Metabolic RegulationShinshu University Graduate School of MedicineMatsumotoJapan
  2. 2.Department of GastroenterologyShinshu University School of MedicineMatsumotoJapan
  3. 3.Department of GastroenterologyShowa Inan General HospitalKomaganeJapan
  4. 4.Department of GastroenterologyIida Municipal HospitalIidaJapan
  5. 5.Department of SurgeryShinshu University School of MedicineMatsumotoJapan
  6. 6.Department of Internal MedicineNagano Red Cross HospitalNaganoJapan

Personalised recommendations