GRUPO OTIMISMO DE APOIO A PORTADORES DE HEPATITE C
ONG - Registro n°.: 176.655 - RCPJ-RJ - CNPJ: 06.294.240/0001-22 - Rio de Janeiro - RJ
Tel.: (21) 9973.6832 - Fax. (21) 2549.8809
e-mail: hepato@hepato.com Internet: www.hepato.com
24/05/2004
Tratamento alternativo em não respondedores
Durante o Digestive Disease Week (DDW 2004) que aconteceu de 15 a 20 de maio de 2004, em New Orleans, Louisiana, Estados Unidos, foram apresentados dois estudos preliminares sobre re-tratamento de pacientes que não responderam ao interferon peguilado, e, pelo inusitado que apresentam, estarei fazendo um breve relato incluindo alguns comentários.
Estes estudos apresentam um tratamento alternativo, com ervas, utilizando Mistletoe Extract (Abnobaviscum) em combinaçao com o Solanum Lycopersicum e o Hepatodoron. v
Bom, parece coisa complicada, assim, considero oportuno esclarecer inicialmente o que são estes `produtos`. O Mistletoe Extract (Abnobaviscum) e uma planta considerada uma parasita, sendo largamente estudada no tratamento do câncer, para o qual se aplica na forma de extrato injetável. O assustador Solanum Lycopersicum e o nosso conhecido tomate, sendo que os estudos empregaram o tomate verde, e o Hepatodoron são umas tabletes de ervas vendidas na Alemanha como estimuladoras da função hepática que contem Vitis Vinifera (folhas de uva) indicada para regular o metabolismo do hidrato de carbono e Fragaria Vesca (folhas de morango) indicadas como um estimulador da função metabólica do fígado, segundo seus fabricantes).
Não devem os infectados com hepatite C sair na rua a procurar estes alternativos, pois ainda não se sabe se existem riscos no seu uso. Os estudos apresentados procuram encontrar alguma alternativa de tratamento, principalmente para quem não responde ao tratamento com o interferon ou para quem não pode fazer uso dele. Acredito que vários pesquisadores irão iniciar estudos sobre esta alternativa.
O Dr. Harald Matthes e sua equipe (Universidade de Charite - Berlim - Alemanha) apresentou um estudo feito na Alemanha com 85 pacientes os quais foram tratados durante 24 meses com injeções subcutâneas de Mistletoe Extract, e cápsulas de Solanum Lycopersicum (tomate verde) e de Hepatodoron.
Após 12 meses de tratamento 18% eram responderes completos (tinham negativado o vírus) 49% eram responderes parciais e 33% eram não-respondedores. Após os 24 meses de tratamento e mais seis meses para se verificar se não existia replicação viral se encontrou que 44% tinham resposta sustentada (vírus indetectável) 28% tinham uma resposta considera parcial e 28% não conseguiram nenhum beneficio.
O Dr. Matthes explicou que o extrato o Mistletoe Extract ativa as células CD4 T induzindo uma resposta ao vírus da hepatite C e o Hepatodoron estimula a regeneração do fígado. O tomate verde contem alcalóides que induzem o apoptoses do caspase 8. "isto é importante porque o vírus da hepatite C obstrui o apoptoses do hepatócito, que é requerido pelas células infectadas do fígado".
Acrescentou ainda que nas primeiras 8 semanas de tratamento foi observada uma elevação das enzimas do fígado, normalizando depois deste período a inflamação do fígado. Ressaltou ainda que o Mistletoe Extract e usado no tratamento de alguns tipos de câncer o que demonstra sua segurança, mas não recomendou a terapia alternativa em pacientes virgens de tratamento, recomendando maiores estudos em pacientes não respondedores ao interferon peguilado, já que o este tratamento ao induzir a apoptoses do hepatócito poderia ser perigoso para pacientes com alto dano hepático.
Um outro estudo apresentado pela equipe do Dr. Friedemann Schad foi realizado com oito pacientes para se estudar a progressão da fibroses, utilizando, também, a combinação das ervas do estudo acima citado.
Dos oitos pacientes em cinco deles foi verificada uma redução no grau de fibroses, um teve progressão no seu grau e dois ficaram estáveis.
Os autores esclarecem que este tratamento deverá ser mais bem estudado, pois poderia ser uma alternativa em pacientes não respondedores ao interferon peguilado ou que por diversos problemas não podem ser tratados com interferon.
Cada vez que divulgo alguma informação neste sentido a quantidade de e-mails de alguns pacientes e até de alguns médicos solicitando maiores informações e enorme, assim, antecipadamente, seguem os Abstract originais (em inglês) apresentados na Digestive Disease Week 2004 realizada entre 15 e 20 de maio de 2004, em New Orleans, Estados Unidos.
OUTCOME STUDY ON HEPATITIS C THERAPY WITH MISTLETOE EXTRACT AND SOLANUM LYCOPERSICUM IN NONRESPONDERS TO INTERFERON/RIBAVIRIN
H Matthes and others. Outcome Study on Hepatitis C Therapy with Mistletoe (Viscum Album L.; Abnobaviscum) and Solanum Lycopersicum. Abstract 82 (poster). Digestive Disease Week. May 15-20, 2004. New Orleans, LA.
Combined therapy with pegylated Interferon-alpha and ribavirin reaches sustained response rates of 45-70%, depending on the genotype. The wide range of side effects often leads to interruption or cessation of therapy.
An alternative herbal therapy consisting of mistletoe extract (Abnobaviscum) in combination with Solanum lycopersicum and Hepatodoron was initiated in patients for whom interferon alfa/ribavirin therapy has failed and high rates of side effects have occurred.
The objective of the current German study is to achieve HCV-RNA-PCR negativity after 1 or 2 years of treatment and 6 months of follow up, documentation of side effects, fibrosis -parameter (PIIIP) and the quantitative course of HCV-RNA-PCR.
Up to now, 85 patients with chronic hepatitis C (> 6 months) with increased transaminases and positive HCV-RNA-PCR values have been included. 43 patients had a liver biopsy before therapy; 27 patients failed interferon therapy. Genotype was determined in all patients.
Initially mistletoe was administered 3 times per week subcutaneously; concomitantly, Hepatodoron 3 x 2 tablets were given. After 14 days Solanum lycopersicum Herba D3-4 tablets were applied. Duration of therapy was 12 (78 patients) - 24 months (64 patients).
RESULTS
78 of 85 patients terminated the therapy. 14 patients (18%) were HCV-RNA-PCR negative after 12 months. After 24 months 20 patients (25%) showed a sustained response. 44 patients (56%) were non-responders. No essential side effects were observed.
Transaminases and PIIIP-values decreased significantly during therapy (p<0,05>). Virus load did not decrease continuously but in those patients with HCV-RNA-PCR negativity it decreased below the limit of detection, independent of the initial level. 2 patients had shown a so-called 'break through' phenomenon.
DISCUSSION
Combined therapy of mistletoe and Solanum lycopersicum showed virus elimination and sustained response in chronic hepatitis C. The advantage of mistletoe therapy is the absence of side effects and its cost effectiveness.
The authors conclude, "Mistletoe therapy could be an alternative in non-responders to standard therapy or in patients with relative or absolute contraindications of interferon therapy. Further studies will be necessary to optimize the therapy and to verify the results."
VISCUM ALBUM L AND SOLANUM LYCOPERSICUM INHIBIT FIBROSIS IN CHRONIC HEPATITIS C (HCV): A PILOT STUDY
Friedemann Schad, Burkhard Matthes, Silke Biesenthal-Matthes, Dirk Buchwald, Harald Matthes
INTRODUCTION
Untreated HCV leads to liver cirrhosis and hepatocellular carcinoma in 20-30% of cases after 25 years of infection. No treatment is known in failure or contraindications to standard therapy (pegylated interferon and ribavirin).
AIM
We investigated the effect on fibrosis in a pilot study using a complementary concept with viscum album L (mistletoe) and herbal extracts of Solanum lycopersicum, Fragaria vesca/Vitis vinifera (Hepatodoron).
METHODS
8 patients with HCV (genotype 1) were treated with Viscum album (ABNOBAviscum aceris or Helixor M) 3 x weekly 1 Amp. sc., Solanum lyc. D4-D6 2-6 Tbl. and Hepatodoron 2-6 Tbl. daily. Mean duration of therapy was 13.3 months. A liver biopsy was conducted before and 6-10 months after treatment and the modified HAI score was calculated and compared with the paired Wilcoxon Test.
RESULTS
In 8 patients (5 female, 3 male; mean age 43, mean duration of HCV 20 years) the HAI score before treatment was 7.75; after 18 - 23 months (>12 months of treatment and 6-11 months follow-up) the score was 5.25 (p=0.05). The fibrosis stage decreased from 2.375 to 1.375 (p=0.09). In 4 patients, fibrosis decreased by 1-3 score points, 1 patient increased by 1 scored point and 3 were stable. Also peri-portal inflammation decreased but not significantly.
DISCUSSION
Progression of fibrosis leads to the natural endpoint of cirrhosis in chronic HCV infection which is the most frequent indication for liver transplantation in western countries. Inhibition or decrease of fibrosis is the leading therapeutic aim in chronic HCV therapy. Interferon therapy inhibits inflammation and fibrosis in the liver. Viscum Album L has shown positive effects on viral load, levels of ASL and ALT and HRQOL in HCV therapy. In cirrhotic livers of rats antioxidative and antifibrotic effects have been seen with solanum lycopersicum. Morphological findings show a significant decrease in total HAI with a decrease in fibrosis due to a decrease of pro-fibrotic cytokines like FGF - ß, TGF - ß and TNF - a found in the liver cells of HCV + patients under viscum album L therapy. In cancer treatment viscum album L decreases tumor in HCC and improves QOL in breast, ovarian and non-small cell lung cancer. It may be discussed that viscum album L has an effect of cancer prevention in HCV infection. Viscum album L is an immunomodulatory and immuno-stimulatory substance which induces apoptosis. Solanum lycopersicum can induce apoptosis in a high amount in HEP G2 cells by stimulation of caspase 8 (FLICE enzyme). Apoptosis is one of the leading mechanisms in hepatic viral clearance in HCV. Both effects may be responsible for decreasing inflammation and fibrosis shown here.
CONCLUSION
Viscum album and the herbal extract were able to inhibit and reduce fibrosis in liver biopsies scored by HAI. This therapy concept might be beneficial to non-responders and patients not compliant with standard HCV therapy. Further studies are necessary to confirm this preliminary data.
GRUPO OPTIMISMO DE AYUDA A PORTADORES DE HEPATITIS C
ONG - Registro n°. 176.655 - RCPJ-RJ - Rio de Janeiro - Brasil
Tel. 55.21 - 9973.6832 - Fax. 55.21 - 2549.8809
e-mail: hepato@hepato.com Internet: www.hepato.com
24/05/2004
Tratamiento alternativo en no respondedores
Durante el Digestive Disease Week (DDW 2004) que aconteció de 15 a 20 de mayo de 2004, en New Orleans, Louisiana, Estados Unidos, fueron presentados dos estudios preliminares sobre se re-tratamiento de pacientes que no respondieron al interferón pegilado, y, por lo inusitado que presentan, estaré haciendo un breve relato incluyendo algunos comentarios.
Estos estudios presentan un tratamiento alternativo, con hierbas, utilizando Mistletoe Extract (Abnobaviscum) combinado con el Solanum Lycopersicum y el Hepatodoron.
Bueno, parece cosa complicada, así, considero oportuno aclarar inicialmente lo que son estos `productos`. El Mistletoe Extract (Abnobaviscum) es una planta considerada una hierba dañina, siendo largamente estudiada en el tratamiento del cáncer, para el cual se aplica en la forma de extracto inyectable El asustador Solanum Lycopersicum es nuestro conocido tomate, siendo que los estudios emplearon el tomate verde, y el Hepatodoron son unas tabletas de hierbas vendidas en Alemania como estimuladoras de la función hepática (contienen Vitis Vinifera (hojas de uva) indicada para regular el metabolismo del hidrato de carbono y Fragaria Vesca (hojas de fresas) indicadas como un estimulador de la función metabólica del hígado, según sus fabricantes).
No deben los infectados con hepatitis C salir a la calle a buscar estos alternativos, pues aún no se sabe se existen riesgos en su uso. Los estudios presentados buscan encontrar alguna alternativa de tratamiento, principalmente para quien no responde al tratamiento con el interferón pegilado o para quien no puede hacer uso del interferón. Creo que varios pesquisidores irán a empezar estudios sobre esta alternativa.
El Dr. Harald Matthes y su equipo (Universidad de Charite - Berlín - Alemania) presentó un estudio hecho en Alemania con 85 pacientes quiénes fueron tratados durante 24 meses con inyecciones subcutáneas de Mistletoe Extract, y cápsulas de Solanum Lycopersicum (tomate verde) y de Hepatodoron.
Después de 12 meses de tratamiento 18% eran respondedores completos (tenían negativado el virus) 49% eran respondedores parciales y 33% eran no respondedores. Después de los 24 meses de tratamiento y más seis meses para verificarse si no existía replicación viral se encontró que 44% tenían respuesta sostenida (virus indetectable) 28% tenían una respuesta considera parcial y 28% no consiguieron ningún beneficio.
El Dr. Matthes explicó que el extracto el Mistletoe Extract activa las células CD4 T induciendo una respuesta al virus de la hepatitis C y el Hepatodoron estimula la regeneración del hígado. El tomate verde contiene alcaloides que inducen la apoptosis del caspase 8. "esto es importante porque el virus de la hepatitis C obstruí la apoptosis del hepatocito, que es requerido por las células infectadas del hígado".
Explico que aunque en las primeras 8 semanas de tratamiento fue observada una elevación de las enzimas del hígado, se normalizando después de este período la inflamación del hígado. Resaltó que el Mistletoe Extract es usado en el tratamiento de algunos tipos de cáncer lo que demuestra su seguridad, pero no recomendó la terapia alternativa en pacientes vírgenes de tratamiento, recomendando mayores estudios en pacientes no respondedores al interferón pegilado, ya que este tratamiento al inducir a apoptosis del hepatocito podría ser peligroso para pacientes con alto daño hepático.
Un otro estudio presentado por el equipo del Dr. Friedemann Schad fue realizado con ocho pacientes para estudiarse la progresión de la fibrosis, utilizando, también, la combinación de las hierbas del estudio arriba citado.
De los ochos pacientes, en cinco de ellos fue verificada una reducción en el grado de fibrosis, uno tuvo progresión en su grado y dos quedaron estables.
Los autores aclaran que este tratamiento deberá ser mejor estudiado, pues podría ser una alternativa en pacientes no respondedores al interferón pegilado o para aquellos que por diversos problemas no pueden ser tratados con interferón.
Cada vez que divulgo alguna información en este sentido la cantidad de e-mails de algunos pacientes y hasta de algunos médicos pidiendo mayores informaciones es enorme, así, anticipadamente, siguen los Abstract originales (en inglés) presentados en la Digestive Disease Week 2004 realizada entre 15 y 20 de mayo de 2004, en New Orleans, Estados Unidos.
OUTCOME STUDY ON HEPATITIS C THERAPY WITH MISTLETOE EXTRACT AND SOLANUM LYCOPERSICUM IN NONRESPONDERS TO INTERFERON/RIBAVIRIN
H Matthes and others. Outcome Study on Hepatitis C Therapy with Mistletoe (Viscum Album L.; Abnobaviscum) and Solanum Lycopersicum. Abstract 82 (poster). Digestive Disease Week. May 15-20, 2004. New Orleans, LA.
Combined therapy with pegylated Interferon-alpha and ribavirin reaches sustained response rates of 45-70%, depending on the genotype. The wide range of side effects often leads to interruption or cessation of therapy.
An alternative herbal therapy consisting of mistletoe extract (Abnobaviscum) in combination with Solanum lycopersicum and Hepatodoron was initiated in patients for whom interferon alfa/ribavirin therapy has failed and high rates of side effects have occurred.
The objective of the current German study is to achieve HCV-RNA-PCR negativity after 1 or 2 years of treatment and 6 months of follow up, documentation of side effects, fibrosis -parameter (PIIIP) and the quantitative course of HCV-RNA-PCR.
Up to now, 85 patients with chronic hepatitis C (> 6 months) with increased transaminases and positive HCV-RNA-PCR values have been included. 43 patients had a liver biopsy before therapy; 27 patients failed interferon therapy. Genotype was determined in all patients.
Initially mistletoe was administered 3 times per week subcutaneously; concomitantly, Hepatodoron 3 x 2 tablets were given. After 14 days Solanum lycopersicum Herba D3-4 tablets were applied. Duration of therapy was 12 (78 patients) - 24 months (64 patients).
RESULTS
78 of 85 patients terminated the therapy. 14 patients (18%) were HCV-RNA-PCR negative after 12 months. After 24 months 20 patients (25%) showed a sustained response. 44 patients (56%) were non-responders. No essential side effects were observed.
Transaminases and PIIIP-values decreased significantly during therapy (p<0,05>). Virus load did not decrease continuously but in those patients with HCV-RNA-PCR negativity it decreased below the limit of detection, independent of the initial level. 2 patients had shown a so-called 'break through' phenomenon.
DISCUSSION
Combined therapy of mistletoe and Solanum lycopersicum showed virus elimination and sustained response in chronic hepatitis C. The advantage of mistletoe therapy is the absence of side effects and its cost effectiveness.
The authors conclude, "Mistletoe therapy could be an alternative in non-responders to standard therapy or in patients with relative or absolute contraindications of interferon therapy. Further studies will be necessary to optimize the therapy and to verify the results."
VISCUM ALBUM L AND SOLANUM LYCOPERSICUM INHIBIT FIBROSIS IN CHRONIC HEPATITIS C (HCV): A PILOT STUDY
Friedemann Schad, Burkhard Matthes, Silke Biesenthal-Matthes, Dirk Buchwald, Harald Matthes
INTRODUCTION
Untreated HCV leads to liver cirrhosis and hepatocellular carcinoma in 20-30% of cases after 25 years of infection. No treatment is known in failure or contraindications to standard therapy (pegylated interferon and ribavirin).
AIM
We investigated the effect on fibrosis in a pilot study using a complementary concept with viscum album L (mistletoe) and herbal extracts of Solanum lycopersicum, Fragaria vesca/Vitis vinifera (Hepatodoron).
METHODS
8 patients with HCV (genotype 1) were treated with Viscum album (ABNOBAviscum aceris or Helixor M) 3 x weekly 1 Amp. sc., Solanum lyc. D4-D6 2-6 Tbl. and Hepatodoron 2-6 Tbl. daily. Mean duration of therapy was 13.3 months. A liver biopsy was conducted before and 6-10 months after treatment and the modified HAI score was calculated and compared with the paired Wilcoxon Test.
RESULTS
In 8 patients (5 female, 3 male; mean age 43, mean duration of HCV 20 years) the HAI score before treatment was 7.75; after 18 - 23 months (>12 months of treatment and 6-11 months follow-up) the score was 5.25 (p=0.05). The fibrosis stage decreased from 2.375 to 1.375 (p=0.09). In 4 patients, fibrosis decreased by 1-3 score points, 1 patient increased by 1 scored point and 3 were stable. Also peri-portal inflammation decreased but not significantly.
DISCUSSION
Progression of fibrosis leads to the natural endpoint of cirrhosis in chronic HCV infection which is the most frequent indication for liver transplantation in western countries. Inhibition or decrease of fibrosis is the leading therapeutic aim in chronic HCV therapy. Interferon therapy inhibits inflammation and fibrosis in the liver. Viscum Album L has shown positive effects on viral load, levels of ASL and ALT and HRQOL in HCV therapy. In cirrhotic livers of rats antioxidative and antifibrotic effects have been seen with solanum lycopersicum. Morphological findings show a significant decrease in total HAI with a decrease in fibrosis due to a decrease of pro-fibrotic cytokines like FGF - ß, TGF - ß and TNF - a found in the liver cells of HCV + patients under viscum album L therapy. In cancer treatment viscum album L decreases tumor in HCC and improves QOL in breast, ovarian and non-small cell lung cancer. It may be discussed that viscum album L has an effect of cancer prevention in HCV infection. Viscum album L is an immunomodulatory and immuno-stimulatory substance which induces apoptosis. Solanum lycopersicum can induce apoptosis in a high amount in HEP G2 cells by stimulation of caspase 8 (FLICE enzyme). Apoptosis is one of the leading mechanisms in hepatic viral clearance in HCV. Both effects may be responsible for decreasing inflammation and fibrosis shown here.
CONCLUSION
Viscum album and the herbal extract were able to inhibit and reduce fibrosis in liver biopsies scored by HAI. This therapy concept might be beneficial to non-responders and patients not compliant with standard HCV therapy. Further studies are necessary to confirm this preliminary data.