Background: This study aimed to investigate the efficacy and safety of a 12-month treatment with Phyllanthus niruri in subjects with chronic hepatitis B virus (HBV) infection. Patients and Methods: A placebo-controlled, parallel-group double-blind trial was performed. Clinical assessments took place at baseline and at 1, 3, 9, and 12 months after the treatment start and 6 months after treatment end. Results: In the first 2 years, 50 eligible subjects with chronic HBV accepted to participate. Of those, 47 completed all the study-related visits (6% drop-out rate): 24 of the 26 (92%) allocated to the Phyllanthus group and 23 of the 24 (96%) allocated to the placebo group completed the study. No statistically significant differences in viral load were found between the intervention and placebo groups after 12 months and no subjects showed HBsAg clearance. With regards to safety, there were no changes in renal function parameters in both groups after 12 months and no serious adverse events occurred due to the treatment. The study was stopped at the end of the second year because there was no apparent benefit of the treatment. Conclusion: This study does not support the use of Phyllanthus niruri for the treatment of chronic hepatitis B.

1.
Ott JJ, Stevens GA, Groeger J, Wiersma ST: Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 2012;30:2212-2219.
2.
World Health Organization: Hepatitis B vaccines. Weekly epidemiological record 2009;40:405-420.
3.
EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012;57:167-185.
4.
Liaw YF, Kao JH, Piratvisuth T, Chan HL, Chien RN, Liu CJ, Gane E, Locarnini S, Lim SG, Han KH, Amarapurkar D, Cooksley G, Jafri W, Mohamed R, Hou JL, Chuang WL, Lesmana LA, Sollano JD, Suh DJ, Omata M: Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int 2012;6:531-561.
5.
Papatheodoridis GV, Tsochatzis E, Hardtke S, Wedemeyer H: Barriers to care and treatment for patients with chronic viral hepatitis in Europe: a systematic review. Liver Int 2014;34:1452-1463.
6.
Stickel F, Schuppan D: Herbal medicine in the treatment of liver diseases. Dig Liver Dis 2007;39:293-304.
7.
Venkateswaran PS, Millman I, Blumberg BS: Effects of an extract from Phyllanthusniruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies. Proc Natl Acad Sci U S A 1987;84:274-278.
8.
Lee CD, Ott M, Thyagarajan SP, Shafritz DA, Burk RD, Gupta S: Phyllanthus amarus down-regulates hepatitis B virus mRNA transcription and replication. Eur J Clin Invest 1996;26:1069-1076.
9.
Ott M, Thyagarajan SP, Gupta S: Phyllanthus amarus suppresses hepatitis B virus by interrupting interactions between HBV enhancer I and cellular transcription factors. Eur J Clin Invest 1997;27:908-915.
10.
Liu S, Wei W, Shi K, Cao X, Zhou M, Liu Z: In vitro and in vivo anti-hepatitis B virus activities of the lignan niranthin isolated from Phyllanthus niruri L. J Ethnopharmacol 2014;155:1061-1067.
11.
Mohan M, James P, Valsalan R, Nazeem PA: Molecular docking studies of phytochemicals from Phyllanthus niruri against Hepatitis B DNA Polymerase. Bioinformation 2015;11:426-431.
12.
Wu Y, Lu Y, Li SY, Song YH, Hao Y, Wang Q: Extract from Phyllanthus urinaria L. inhibits hepatitis B virus replication and expression in hepatitis B virus transfection model in vitro. Chin J Integr Med 2015;21:938-943.
13.
Thyagarajan SP, Subramanian S, Thirunalasundari T, Venkateswaran PS, Blumberg BS: Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. Lancet 1988;2:764-766.
14.
Thyagarajan SP, Jayaram S, Valliammai T, Madanagopalan N, Pal VG, Jayaraman K: Phyllanthus amarus and hepatitis B. Lancet 1990;336:949-950.
15.
Leelarasamee A, Trakulsomboon S, Maunwongyathi P, Somanabandhu A, Pidetcha P, Matrakool B, Lebnak T, Ridthimat W, Chandanayingyong D: Failure of Phyllanthus amarus to eradicate hepatitis B surface antigen from symptomless carriers. Lancet 1990;335:1600-1601.
16.
Liu J, Lin H, McIntosh H: Genus Phyllanthus for chronic hepatitis B virus infection: a systematic review. J Viral Hepat 2001;8:358-366.
17.
Xia Y, Luo H, Liu JP, Gluud C: Phyllanthus species for chronic hepatitis B virus infection. Cochrane Database Syst Rev 2011;(4):CD008960.
18.
Xia Y, Luo H, Liu JP, Gluud C: Phyllanthus species versus antiviral drugs for chronic hepatitis B virus infection. Cochrane Database Syst Rev 2013;(4):CD009004.
19.
Wong GL, Tse YK, Wong VW, Yip TC, Tsoi KK, Chan HL: Long-term safety of oral nucleos(t)ide analogs for patients with chronic hepatitis B: a cohort study of 53,500 subjects. Hepatology 2015;62:684-693.
20.
Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G, Flaherty JF, Aguilar Schall R, Bornstein JD, Kitrinos KM, Subramanian GM, McHutchison JG, Heathcote EJ: Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet 2013;381:468-475.
21.
Chang TT, Liaw YF, Wu SS, Schiff E, Han KH, Lai CL, Safadi R, Lee SS, Halota W, Goodman Z, Chi YC, Zhang H, Hindes R, Iloeje U, Beebe S, Kreter B: Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology 2010;52:886-893.
22.
de Franchis R, Hadengue A, Lau G, Lavanchy D, Lok A, McIntyre N, Mele A, Paumgartner G, Pietrangelo A, Rodes J, Rosenberg W, Valla D; EASL Jury: EASL International Consensus Conference on Hepatitis B. 13-14 September, 2002 Geneva, Switzerland. Consensus statement (long version). J Hepatol 2003;39(Suppl 1):S3-25.
23.
Gaeta GB, Stornaiuolo G, Precone DF, Lobello S, Chiaramonte M, Stroffolini T, Colucci G, Rizzetto M: Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. A multicenter Italian study. J Hepatol 2003;39:1036-1041.
24.
Zarski JP, Marcellin P, Leroy V, Trepo C, Samuel D, Ganne-Carrie N, Barange K, Canva V, Doffoel M, Cales P: Characteristics of patients with chronic hepatitis B in France: predominant frequency of HBe antigen negative cases. J Hepatol 2006;45:355-360.
25.
Fattovich G: Natural history and prognosis of hepatitis B. Semin Liver Dis 2003;23:47-58.
26.
Carosi G, Rizzetto M, Alberti A, Cariti G, Colombo M, Craxi A, Filice G, Levrero M, Mazzotta F, Pastore G, Piccinino F, Prati D, Raimondo G, Sagnelli E, Toti M, Brunetto M, Bruno R, Di Marco V, Ferrari C, Gaeta GB, Lampertico P, Marzano A, Pollicino T, Puoti M, Santantonio T, Smedile A: Treatment of chronic hepatitis B: update of the recommendations from the 2007 Italian Workshop. Dig Liver Dis 2011;43:259-265.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.