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| Alternate Therapies |
Alternative Medicine for Chronic Liver Disease.
Leonard B. Seeff, MD, from the National Institute of Health (NIH) in Bethesda, Maryland, gave a report on the recent NIH Symposium focusing on the issue of botanical preparations and herbal preparations available to treat chronic liver diseases. He spoke at the postgraduate course in Dallas held in conjunction with the annual meeting of the American Association for the Study of Liver Disease (AASLD).
Dr. Seeff presented data showing that most patients with chronic liver disease use some type of alternative medicine products and that "conventional" Western science needs to examine these products to find out which ones are effective and helpful and which ones may be harmful. He pointed out some herbal products that appeared to be beneficial and deserve further study.
Some of the potentially beneficial herbal products listed by Dr Seeff included milk thistle and sho-saiko-to (TJ-9) as mentioned above. In addition, he noted that Glycyrrhizin (licorice root extract), a product used in Japan for the treatment of hepatitis, appears to have anti-inflammatory properties and improves ALT levels when given intravenously. Some studies have been reported using glycyrrhizin in pill form for the treatment of viral hepatitis. One study gave interferon only or interferon plus glycyrrhizin to patients that had failed to respond to interferon. ALT levels normalized in 33% of those receiving interferon only, but in 64% of those receiving the glycyrrhizin in addition to the interferon. HCV-RNA became undetectable in 38.5% of those receiving the herbal product, but in only 13% of those treated with interferon only.
Another interesting product is Compound 861. This is a liquid medicine that contains 10 herbs based on traditional Chinese medicine. This compound appears to be anti-fibrotic (prevents or improves the scar tissue in the liver). A study in China gave this compound to patients with hepatitis B and found improvement in most patients.
The NIH has allocated funds to be used for research related to herbal products. Hopefully we will soon be able to tease out those products that are effective from those who may not help at all or even be harmful.
Alternative therapy for hepatitis C.
Since the 1997 NIH Consensus Development Conference on the Management of Hepatitis C, several important therapeutic advances have occurred, particularly with the introduction of PEG-interferon with ribavirin therapy. Combination therapy results in better treatment responses than monotherapy. The highest response rates have been achieved with PEG-interferon in combination with ribavirin. Genotype determinations now influence treatment decisions. Methods of genotyping include PCR-based techniques and, more recently, less expensive serotyping (antibody) assays. Sustained viral response (SVR), defined by the absence of detectable qualitative HCV RNA in the serum by RT-PCR 24 weeks after the end of treatment, is currently the best indicator of effective therapy.
Treatment of Naпve Patients
Three large pivotal trials have examined the efficacy of PEG-interferon plus ribavirin in the treatment of chronic HCV infection. These trials excluded patients with decompensated cirrhosis and other comorbid conditions. Overall, PEG-interferon plus ribavirin is more effective than standard interferon-ribavirin combination or PEG-interferon alone. SVRs were similar with both forms of PEG-interferon (alpha 2a and alpha 2b) when used in combination with ribavirin.
Factors associated with successful therapy include genotypes other than 1, lower baseline viral load, and less fibrosis or inflammation on liver biopsy. In all three trials, an SVR of 42 to 46 percent was achieved for genotype 1 using a higher dose of PEG-interferon and ribavirin for 48 weeks. An SVR of 76 to 82 percent was achieved for patients with genotypes 2 and 3. It appears that 24 weeks of treatment and a lower dose of ribavirin is adequate for genotypes 2 and 3. Early viral response (EVR), defined as a minimum 2 log decrease in viral load during the first 12 to 24 weeks of treatment, has been identified as predictive of SVR. Those who fail to achieve an EVR have only a small chance of achieving a SVR even if therapy is continued for a full year.
Although SVR has not yet been correlated with improved survival because of the necessity for long-term followup, the absence of a detectable serum HCV RNA has been correlated with resolution of liver injury, reduction in hepatic fibrosis, and a very low likelihood of recurrent HCV infection. Additionally, in two large recent studies from Japan, interferon treatment was associated with a reduction in the development of hepatocellular carcinoma, a finding that was more pronounced among patients with SVR.
Re-treatment of Patients
Patients who may benefit from re-treatment include those whose HCV infection failed to achieve SVR. Decisions regarding re-treatment should be based upon: (1) previous type of response, (2) the previous therapy and the difference in potency of the new therapy, (3) the severity of the underlying liver disease, (4) viral genotype and other predictive factors for response, and (5) tolerance of previous therapy and adherence.
Relapsers achieve an initial end of treatment response (ETR) for their HCV disease, but it is not sustained over time (i.e., no SVR). Non-Responders never achieve an EVR, ETR, or SVR.
Among the non-responders, there is a subset of persons who have a substantial reduction of HCV RNA (1 to 2 log units or more) during therapy, and who can be categorized as partial responders. Even in the absence of SVR, treatment may be associated with improved histology.
Preliminary results suggest that overall only 15 to 20 percent of non-responders treatedwith standard interferon/ribavirin combinations achieved an SVR on re-treatment using PEG-interferon with ribavirin. Patients with genotypes 2 or 3 have better response rates to re-treatment than genotype 1.
The ability to achieve SVR following re-treatment with PEG-interferon/ribavirin in patients who relapsed following interferon monotherapy or standard interferon/ribavirin therapy is currently being evaluated. However, in cases where the same regimen has been used for re-treatment, virtually all patients relapse again after treatment is stopped. Extending the duration of re-treatment without changing the dose or regimen may reduce the relapse rate, but this has not yet been proven prospectively.
Patients whose HCV infection does not respond to the current optimal therapy with PEG- interferon and ribavirin present a significant problem, particularly in the presence of advanced fibrosis or cirrhosis. The possible role of maintenance therapy with PEG-interferon alone in preventing further progression of cirrhosis, clinical decompensation, or development of hepatocellular carcinoma is currently the focus of a large-scale, multicenter United States trial, HALT-C. Until the results of HALT-C or similar studies are available, the role of long-term, continuous therapy with PEG-interferon (or ribavirin or both) for non-responders must be considered experimental.
Knowledge of the severity of the underlying liver disease is important in recommending re-treatment. Patients with advanced fibrosis or cirrhosis are at increased risk for developing hepatic decompensation and should be considered for re-treatment, especially if they were originally treated with interferon monotherapy. For the re-treatment of patients with intermediate degrees of fibrosis and disease activity, clinicians should consider the factors enumerated above. |
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