Intervention Review

Phyllanthus species for chronic hepatitis B virus infection

  1. Yun Xia1,*,
  2. Hui Luo2,
  3. Jian Ping Liu3,
  4. Christian Gluud4

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 13 APR 2011

Assessed as up-to-date: 30 OCT 2010

DOI: 10.1002/14651858.CD008960.pub2

Database Title

Additional Information

How to Cite

Xia Y, Luo H, Liu JP, Gluud C. Phyllanthus species for chronic hepatitis B virus infection. Cochrane Database of Systematic Reviews 2011, Issue 4. Art. No.: CD008960. DOI: 10.1002/14651858.CD008960.pub2.

Author Information

  1. 1

    b) Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, a) Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China, Copenhagen, Denmark

  2. 2

    Beijing University of Chinese Medicine, Centre for Evidence-Based Chinese Medicine, Beijing, Chaoyang District, China

  3. 3

    b) National Research Centre in Complementary and Alternative Medicine (NAFKAM), Tromsø, Norway, c) Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, a) Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China, Copenhagen, Denmark

  4. 4

    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Cochrane Hepato-Biliary Group, Copenhagen, Denmark

*Yun Xia, a) Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China, b) Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, 11 Bei San Huan Dong Lu, Chaoyang District, 100029 Beijing, China; Department 3344, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9,, Copenhagen, DK-2100, Denmark. xiayun_xy@126.com.

Publication History

  1. Publication Status: New
  2. Published Online: 13 APR 2011

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen

Background

Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists.

Objectives

To evaluate the benefits and harms of phyllanthus species for patients with chronic HBV infection.

Search methods

Searches were performed in The Cochrane Hepato-Biliary Gorup Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and the Chinese Biomedical CD Database, China Network Knowledge Information, Chinese Science Journal Database, TCM Online, and Wanfang Database. Conference proceedings in Chinese were handsearched. All searches were conducted until October 2010.

Selection criteria

Randomised clinical trials comparing phyllanthus species with placebo or no intervention for patients with chronic HBV infection. Co-interventions were allowed if all comparison groups had received the same co-interventions. We included trials irrespective of blinding, publication status, or language.

Data collection and analysis

Two authors selected the trials and extracted the data independently. The RevMan software was used for statistical analysis of dichotomous data with risk ratio (RR) with 95% confidence intervals (CI). Risk of bias was assessed to control for systematic errors. Trial sequential analysis was used in order to control for random errors.

Main results

A total of 16 randomised trials with 1326 patients were included. One trial with 42 participants compared phyllanthus with placebo. The trial found no significant difference in HBeAg seroconversion after the end of treatment (RR 0.9; 95% CI 0.73 to 1.25) or follow-up (RR 1.00; 95% CI 0.63 to 1.60). No other outcomes could be assessed. Fifteen trials compared phyllanthus plus an antiviral drug like interferon alpha, lamivudine, adefovir dipivoxil, thymosin, vidarabine, or conventional treatment with the same antiviral drug alone. Phyllanthus did significantly affect serum HBV DNA (RR 0.69; 95% CI 0.52 to 0.91, P = 0.008; I2 = 71%), serum HBeAg (RR 0.70; 95% CI 0.60 to 0.81, P < 0.00001; I2 = 68%), and HBeAg seroconversion (RR 0.77; 95% CI 0.63 to 0.92, P = 0.005; I2 = 78%), but the heterogeneity was substantial. The result obtained regarding serum HBV DNA was not supported by trial sequential analysis. None of the trials reported mortality and hepatitis B-related morbidity, quality of life, or liver histology. Only two trials reported adverse events with numbers without significant differences. No serious adverse events were reported.

Authors' conclusions

There is no convincing evidence that phyllanthus compared with placebo benefits patients with chronic HBV infection. Phyllanthus plus an antiviral drug may be better than the same antiviral drug alone. However, heterogeneity, systematic errors, and random errors question the validity of the results. Clinical trials with large sample size and low risk of bias are needed to confirm our findings. Species of phyllanthus should be reported in future trials, and a dose-finding design is warranted.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen

Phyllanthus species for chronic hepatitis B virus infection

Chronic hepatitis B virus (HBV) infection causes significant mortality, morbidity, and economic burden worldwide. Although the current approved therapies are effective, response to treatment is not satisfactory. Patients are at high risk of developing viral resistance, and serious adverse events occur. The objective of this review was to evaluate the benefits and harms of phyllanthus species for patients with chronic HBV infection. Phyllanthus species appear to be safe and may potentially have effects on the clearance of viral markers in patients with HBV infection. However, all of the trials evaluated in this review were of low methodology quality, ie, have high risk of bias, and there was a risk of random errors in the majority of comparisons. Furthermore, all analyses showed substantial heterogeneity. Accordingly, randomised clinical trials with low risk of bias and large sample size should be conducted to confirm the effects of phyllanthus species before clinical use is considered.

 

Resumen

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen

Antecedentes

Especies de Phyllanthus (flor de hoja) para la infección crónica por el virus de la hepatitis B

Las especies de Phyllanthus para pacientes con infección crónica por el virus de la hepatitis B (HBV) se han evaluado en ensayos clínicos, pero no existe consenso con respecto a su utilidad.

Objetivos

Evaluar los efectos beneficiosos y perjudiciales de las especies de Phyllanthus en pacientes con infección crónica por el HBV.

Estrategia de búsqueda

Se hicieron búsquedas en el Registro de Ensayos Controlados del Grupo Cochrane Hepatobiliar (Cochrane HepatoBiliary Group), Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) (CENTRAL) en The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, y en la Chinese Biomedical CD Database, China Network Knowledge Information, Chinese Science Journal Database, TCM Online y Wanfang Database. Se hicieron búsquedas manuales en las actas de congresos en chino. Todas las búsquedas se realizaron hasta octubre de 2010.

Criterios de selección

Ensayos clínicos aleatorios que compararan las especies de Phyllanthus con placebo o ninguna intervención en pacientes con infección crónica por el HBV. Se permitieron cointervenciones siempre que todos los grupos de comparación hubieran recibido las mismas cointervenciones. Se incluyeron ensayos independientemente del cegamiento, estado de publicación o idioma.

Obtención y análisis de los datos

Dos autores seleccionaron los ensayos y extrajeron los datos de forma independiente. Para el análisis estadístico de los datos dicotómicos se utilizó el programa informático RevMan, con el cociente de riesgos (CR) y los intervalos de confianza (IC) del 95%. Se evaluó el riesgo de sesgo para controlar los errores sistemáticos. Se utilizó el análisis secuencial de ensayos para controlar los errores aleatorios.

Resultados principales

Se incluyó un total de 16 ensayos aleatorios con 1326 pacientes. Un ensayo con 42 participantes comparó Phyllanthus con placebo. El ensayo no encontró diferencias significativas en la seroconversión del HBeAg después del final del tratamiento (CR 0,9; IC del 95%: 0,73 a 1,25) ni en el seguimiento (CR 1,00; IC del 95%: 0,63 a 1,60). No se pudieron evaluar otros resultados. Quince ensayos compararon Phyllanthus más un fármaco antiviral como el interferón alfa, la lamivudina, el dipivoxil de adefovir, la timosina, la vidarabina o el tratamiento convencional con el mismo fármaco antiviral solo. Phyllanthus afectó significativamente el ADN del VBH sérico (CR 0,69; IC del 95%: 0,52 a 0,91; p = 0,008; I2 = 71%), el HBeAg sérico (CR 0,70; IC del 95%: 0,60 a 0,81; p < 0,00001; I2 = 68%), y la seroconversión del HBeAg (CR 0,77; IC del 95%: 0,63 a 0,92; p = 0,005; I2 = 78%), pero la heterogeneidad fue significativa. El resultado obtenido con respecto al ADN del HBV sérico no fue apoyado por el análisis secuencial de los ensayos. Ninguno de los ensayos informó la mortalidad ni la morbilidad relacionada con la hepatitis B, la calidad de vida ni la histología hepática. Sólo dos ensayos informaron eventos adversos y no hubo diferencias significativas en los números. No se informaron eventos adversos graves.

Conclusiones de los autores

No existen pruebas convincentes de que el Phyllanthus en comparación con placebo beneficie a los pacientes con infección crónica por el HBV. Phyllanthus más un fármaco antiviral puede ser mejor que el mismo fármaco antiviral solo. Sin embargo, la heterogeneidad, los errores sistemáticos y los errores aleatorios cuestionan la validez de los resultados. Se necesitan ensayos clínicos con un tamaño de muestra grande y bajo riesgo de sesgo para confirmar estos hallazgos. En los ensayos futuros se deben informar las especies de Phyllanthus y se justifica un diseño para encontrar la dosis.

Traducción

Traducción realizada por el Centro Cochrane Iberoamericano

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