HEPATITIS C:
Recent Treatment Strategies
Viral hepatitis has been a major human disease for at least 2,000 years. It is estimated that 15% or more of persons living in Southeast Asia and Japan are infected by hepatitis B, a retrovirus that frequently leads to chronic infection. The high incidence of viral infection is the most likely reason that liver cancer and liver cirrhosis have been two of the leading causes of death in China during recent decades (when records were kept). In Japan, hepatitis is cited as the primary reason that medical doctors prescribe Chinese herbs. Minor Bupleurum Combination (Xiao Chaihu Tang) as well as numerous other traditional prescriptions for treating symptoms characteristic of viral hepatitis have been administered and claimed to alleviate symptoms.
When persons who die from liver disease in S.E. Asia are checked for hepatitis B, the virus is found in about 80-85% of cases, indicating that fatal liver diseases mainly arise from chronic infection by hepatotropic viruses. Most of the investigation of hepatitis B has been undertaken for specific research projects, evaluating the role of the disease in China's overall health problems, or the efficacy of various treatments. Until recently, it was relatively rare to test patients for hepatitis B as a matter of course in evaluating health complaints, and it is still not frequent practice.
It is only very recently that Chinese doctors began checking patients for hepatitis C, a virus that was isolated only a decade ago. It is now found to be a common viral infection in China, though not as prevalent as hepatitis B. A substantial proportion of patients with chronic liver disease who are tested are found to harbor both hepatitis B and hepatitis C. As with hepatitis B, testing for hepatitis C is mainly undertaken for specific research projects, not general health care.
The infection is also fairly common in the United States: hepatitis C is currently estimated to infect at least 3.5 million in the U.S., perhaps having been a factor in the death of 100,000 Americans already (mainly during the past decade). Hepatitis C now accounts for an estimated 150,000 newly diagnosed cases of viral hepatitis each year, while many cases continue to go undiagnosed. Approximately 10,000 people die annually from liver disease that is attributed to hepatitis C (liver diseases of all types kill about 40,000 people per year in the U.S. and much of this is now understood to be due to the presence of chronic viruses). About 1,000 people each year receive a liver transplant because of cirrhosis caused by hepatitis C, and the numbers would be higher if there were more livers made available for transplant.
The hepatitis C virus was not detectable until a test for it was developed in 1989. Prior to that, cases of hepatitis that could neither be explained by the then-known viral strains (A and B) nor as an evident result of drug side effects were described as non-A, non-B hepatitis. Hepatitis C (as well as numerous other hepatic viruses) is now known to be the main cause of non-A, non-B hepatitis. This virus has been spread by blood transfusions for at least three decades (see below), persisting in the blood supply for several years after hepatitis B was removed. The hepatitis B test was applied to all collected blood since the 1970's; hepatitis C is no longer in the donated blood supply, having been eliminated by routine testing since 1990.
Hepatitis C is thought to be transmitted almost solely by direct blood contact. However, surveys of hepatitis C patients indicate that up to one in six cases might be caused by sexual contact with an infected person, and there appear to be cases where people living in the same home but having no sexual intimacy with an infected person can pick up the disease (accounting for up to one in ten infections). Most of the unexplained cases of hepatitis C transmission might actually involve some kind of less evident blood to blood transmission. It is suspected that blood contacts occur more often than people realize-sexual contact when there are lesions caused by other infections, tattooing or ear piercing under less than sanitary conditions, sharing of razors or toothbrushes, and during treatment of minor wounds.
The practice of sharing contaminated needles during illicit IV drug use is presently the main route by which the hepatitis C virus is efficiently spread. There have been three decades of increasing levels of IV drug use in the U.S., mainly in the inner cities, and more heavily among African-Americans. Despite increased attention to the health hazards involved with sharing needles, the practice continues. Recent reports indicate that more than 85% of IV drug users are now infected by hepatitis C. About one-third of all people coming to inner-city hospitals have hepatitis C, though the disease is found to some extent in all social classes, all geographic locations, and in all age groups. From the large pool of infected IV drug users it may be spread by sexual contacts as explained above. It is also transmitted from mother to child.
Evidence for hepatitis C infection is not obtained as part of routine medical screening. Even the liver enzyme tests that would indicate some degree of liver inflammation are still not standard in the CBC (complete blood count) ordered by many physicians during medical visits, so asymptomatic patients may go undiagnosed for years. While some people experience an acute hepatitis syndrome upon infection, which might lead one to be tested, that is not the usual situation. Acute hepatitis may manifest as a digestive disturbance that can be taken for "stomach flu," so that testing during the initial phase of disease is still not common. Even when measured, elevated liver enzymes are sometimes attributed to drinking of alcohol, which is a very common practice; in fact, the elevation might be caused by a virus and only exacerbated by the alcohol. Furthermore, some persons with active hepatitis C show only very mild elevations of liver enzymes, at levels for which doctors usually don't express concern. In some cases the disease is not detected until there is need for a liver transplant (a similar situation existed with HIV infection, in which some individuals were unaware of the infection until experiencing a life-threatening case of pneumonia).
It is estimated that the interval from time of infection to time of significant liver cirrhosis, if that is to occur at all, is 20 to 30 years. The delayed expression of the disease is one reason why hepatitis C seems to be a sudden epidemic; another reason is the recent introduction of testing and the new awareness by medical doctors of the importance of testing (now that there are treatments available to administer when the virus is detected).
A likely explanation for the current epidemic of hepatitis C in the U.S. is that the virus was brought to the U.S. primarily from Vietnam, mainly during the period 1964-1973. It may have been brought home by just a few hundred American soldiers (among the hundreds of thousands who served there) and then spread, silently, in the absence of diagnostics and with the normal delay in causing obvious liver disease.
A number of Vietnam veterans had blood transfusions during the war, were exposed to blood on the battlefield or at medical stations, had sexual relations with the Vietnamese, and/or used IV drugs (while in Vietnam or with other veterans after returning). Therefore, opportunities for transmission of a virus that existed in Vietnam were certainly present. Once the virus arrived in the U.S., there were opportunities for it to spread to non-veterans.
Blood transfusions in standard surgical practice were often administered without the patient ever being aware of the fact, or, at least, concerned about it. Thus, an individual diagnosed today with hepatitis C may not realize that they could have been infected when, for example, they had an operation 20 years ago and received blood from someone who carried the virus. Individuals who experimented with non-IV illicit drugs and tried an IV drug even once long ago may have been infected by the virus then; these individuals do not consider themselves IV drug users and may not regard the old incident as an actual example of IV drug use.
During the 1960's and thereafter there was a "sexual revolution" in the United States that led to a large percentage of the teen and adult population having numerous sexual partners within a short period of time. This situation produced waves of STD's, including herpes simplex, gonorrhea, chlamydia (the most frequently reported STD today), and HIV. A person who was infected by hepatitis C virus in the 1960's or 1970's might not easily associate a currently diagnosed case of chronic hepatitis C with sexual behavior of recent memory. Since it appears that sexual transmission of hepatitis C is very inefficient (it does not occur with notable frequency between marriage partners), it is most likely that this virus was only transmitted when there was unrecognized blood transmission, for example if there was an STD that caused lesions, permitting transmission to and from broken blood vessels. Many times, lesions are not obvious (especially in women), but they nonetheless serve to promote viral disease transmission. The rate of hepatitis C among unmarried persons with multiple sexual partners is about twice as high as that of the general population, implying a role for other STD's in hepatitis C transmission via sex, though this increased infection rate may also be due to a higher prevalence of IV drug use among these individuals, with little role of sexual transmission.
Unlike HIV infection, which has been spread in the U.S. since 1976, hepatitis C does not appear to occur with much greater frequency in the male homosexual population than among others in the U.S. This surprises some researchers, and is sometimes explained by the low rate of sexual transmission of the virus, but it can be explained by several factors. If hepatitis C was originally acquired by and spread among a mainly heterosexual population (U.S. armed forces) and brought to the U.S. where it was transmitted primarily by blood transfusion, and to a lesser extent by sexual contact (initially being primarily heterosexual) and within households, then the disease would be seen with considerable frequency outside the male homosexual community. Of course, it could spread easily within that community as well, but if it were already in the other population subgroups, then there would be a more even distribution (as occurs with HIV infection in Africa). This distribution would seem reasonable with the relatively higher level of transmission via medical blood transfusion and IV drug use compared to sexual or other routes of transmission. Further, since hepatitis C was not detectable until recently, and since a large portion of the homosexual men who were involved with multiple sexual partners or with IV drug use experienced HIV infection and its symptoms, testing of these individuals for hepatitis C may simply not have occurred. Hepatitis C testing has not been a priority among medical doctors dealing with AIDS. Already, over 350,000 people have died of AIDS, the majority being homosexual men, most of them not tested for hepatitis C because the focus of testing and treatment was elsewhere. Further, HIV infection is often fatal within 15 years; less time than it usually takes for hepatitis C to cause obvious liver disease.
It is not yet reported whether hepatitis C is unusually prevalent in Vietnam, but it is known that the prevalence is fairly high in nearby Taiwan, and it is evidently fairly widespread in mainland China. Significantly, hepatitis C is frequently found in Vietnam veterans who visit the VA hospitals (although this high rate could be the result of IV drug use after returning to the U.S.) The rate of hepatitis C infection in France is nearly twice that of the U.S,. or of neighboring Germany and about four times that of Australia: French soldiers fought in Vietnam during the 1950's, just prior to American involvement (giving more time for it to spread), which might explain this apparent anomaly.
In a study of stored American blood samples from World War II, hepatitis B-but not hepatitis C-was found. While hepatitis C probably existed at that time (and troops stationed in S.E. Asia may have been exposed), it was probably not as prevalent then and there may have been less chance to either pick it up or to transmit it to others.
At this time, little is known about its pathogenesis following initial infection, except that the infection may remain without presenting evident symptoms for many years. The virus may impact quality of life, but the signs are not taken as evidence of a problem of hepatitis. Whether or not hepatitis C leads to significant liver disease in an individual may depend on secondary factors, such as the presence and activation of other viruses, especially herpes viruses (e.g., EBV, CMV, herpes simplex, HHV-6, HHV-7). Also the action of liver stressors, such as exposure to toxic chemicals in the work place, consumption of alcohol and/or drugs (prescribed or otherwise), or emotional disturbance, might stimulate the viral activity. It is known that for HIV infection, activation of a herpes virus can cause the viral load (amount of virus in the blood) to increase by up to five times (and then decline some time after the herpes returns to dormancy); it is possible that hepatitis C viral load (levels under 100,000/ml are considered low at this time) is also affected by transactivation (one virus activating another). Herpes viruses generally influence the retroviruses.
In the absence of effective treatments, the number of deaths due to advanced liver disease is likely to increase markedly as a result of the spread of both hepatitis B and hepatitis C viruses during the past couple of decades (as with hepatitis C, there is often a twenty year gap between infection by hepatitis B and manifestation of a life-threatening disease). One reason that there are not more deaths by liver disease is that many of those infected by hepatitis viruses succumb first to cardiovascular diseases or to cancers that start somewhere other than the liver. Much of this death is attributed to such common practices cigarette smoking and consuming high levels of dietary fat. It is possible that, since viral hepatitis can alter blood coagulation properties and reduces immune functions, the viral disease actually enhances the chance of death by these other diseases without being formally recognized as a cause.
It has been suggested that nearly all persons exposed to hepatitis C virus become chronically infected (rather than having an acute disease that resolves entirely) and that up to 60% develop chronic liver disease marked by elevated liver enzyme levels if they live through other hazards long enough. However, there are estimates that as few as 9% of hepatitis C infections will become serious (life-threatening), taking all factors into account. Liver cirrhosis and liver cancer are two major disease outcomes. Hepatitis B causes premature death in about 20% of those chronically infected and this is probably about the rate at which hepatitis C will prove fatal. For the other 80%, the consequence of infection is either minor or overshadowed by other diseases.
The concept of cure in a case of an infectious disease, like hepatitis C, includes the complete elimination of the virus from the body, not just limitation of its action (remission). For this concept to be applied, one requires the modern knowledge of, and testing for, viral particles, something that has become common place only during the past few years. The PCR (polymerase chain reaction) test for hepatitis C viral RNA is, therefore, the current standard for measuring the status of the disease, and the determination method of a true cure. The test measures the "viral load," or the quantity of virus in the bloodstream. In someone who is cured, the viral load should be undetectable (technically, one cannot measure tiny amounts of virus, so one can only say below the limit of detection) and then continue to remain undetectable in the absence of any virus suppressing therapies for several years. At this time, it is not known whether hepatitis C can be cured according to this strict standard, partly because there hasn't been enough time (since testing was developed) to determine whether any treatment has a long-term successful result. Interferon treatment produces an effective and prolonged response (up to about three years thus far monitored, but not necessarily a cure) in only 20-30% of those who try it, and it causes significant side effects in many. In fact, several participants in interferon studies withdrew during the first month of treatment (usual duration of treatment is six months). Recently, a combination of ribavirin and interferon has been offered; it appears more effective in lowering viral load than interferon alone (40% effective rate, with up to two years remission measured thus far), but the side effects are even greater, as ribavirin can cause significant bone-marrow suppression.
Currently, a viral load (before treatment) of below 100,000 is considered on the low side; this level is usually accompanied by few, if any, symptoms. A viral load of several million is possible and is usually found in persons with significant symptoms and signs of the hepatic disease. However, individuals who have undergone various treatments have reported alleviation of symptoms while viral load measurements remain quite high, so the viral load is not necessarily a good correlate to the symptomatology.
The immune system responds to viral hepatitis with, among other things, antibodies. These antibodies are generated, usually, when the virus is highly active, but may disappear when the virus is at low levels. Antibody tests are far less expensive than PCR tests, so one may measure whether the antibody test shows positive (indicating active virus with immune response to it) or negative (indicating less activity, with reduced immune response) as a cheaper evaluation tool. Converting from antibody positive to negative has been used in the past as a signal for "cure" of the disease, but we now know that this is not reliable.
Elevated liver enzymes, the signifier of liver inflammation, are caused by so many things (including recent use of the over the counter drug acetominophen) that unless the levels are quite high most physicians ignore them. However, given the extent of the viral hepatitis epidemic and its potential harm, it may be prudent to check for viral hepatitis when liver enzymes are found to be elevated. This viral assay can also be used to help confirm or refute the possibility that a drug or herb therapy is causing hepatic inflammation. In persons with viral hepatitis, elevated liver enzymes are usually a signal that the virus is replicating, destroying liver cells, and releasing the liver cell enzymes into the blood stream. The test for the enzymes (usually ALT, AST, and GGT, though other enzymes can be monitored) is less expensive and easier than antibody testing, and is used to monitor the health of the liver. If the liver enzyme levels in the blood are high and then become reduced after a treatment, this is taken as a sign of inhibition of the viral activity; still, the liver may become less inflamed while the virus remains active, so it is not a sure sign of viral inhibition. Normalization of liver enzymes will almost always correlate with freedom from symptoms of viral hepatitis, and may be interpreted as a "cure" only in the sense of freedom from clinical complaints. However, as with the antibody testing, this test only means that the viral activity is reduced, not that the virus is eliminated.
Liver biopsies are used to determine the extent of damage to the liver; in particular, this test will reveal the extent of fibrosis and fatty deposits. Such tests do little to indicate specific treatment strategies, with two exceptions: persons who have denied (due to limited health impact of the disease) that hepatitis C needs to be aggressively treated may change their minds if they find that their liver has been significantly damaged, and persons who show very extensive liver damage may be put on the list to receive a liver transplant (which is only warranted when the extent of liver damage is great).
The Western medical approach to hepatitis C follows the model used for hepatitis B: the main focus is to avoid infection in the first place, by screening the transfusion blood supply, determining transmission-risk behaviors and warning the population about them, and eventually developing a vaccine for those at risk (e.g., medical workers who may be exposed to blood). Development of a vaccine may be difficult because the hepatitis C virus mutates rapidly; so far, at least six subtypes have been identified. Further, within the blood of an individual patient, several different genome sequences are found, indicating that specific viral inhibitors-as well as vaccines-may be of limited value, similar to the situation with HIV. Post-infection treatment of hepatitis C mainly relies on various types of interferons (alpha interferon derivatives are common), alone or in combination with antiviral drugs (such as ribavirin). New drugs regimens are in various stages of research and development. In advanced cases, liver transplant becomes essential to saving the life of the patient.
Physicians in China were alerted to hepatitis C mainly through the international medical literature. Due to the lesser availability of funds for testing compared to the situation for American and European doctors, Chinese physicians primarily investigate hepatitis C and its treatment in patients who are notably symptomatic for the disease and are seeking relief of symptoms. By contrast, many tens of thousands of Americans with asymptomatic disease may seek treatment simply because the virus showed up after routine examination indicated mildly elevated liver enzymes. Because Chinese doctors mainly deal with symptomatic patients and because testing of these patients is also limited, the analysis of symptoms and the alleviation of symptoms are a primary concern. For traditional doctors, the fact that the virus now involved is "C" rather than "B" has little significance in relation to treatment. Rather, the important factors are the symptom manifestation and the fact, known from modern science, that a virus is involved.
In an article by Chen Lihua (1), a traditional Chinese medical analysis of hepatitis C was presented. The author makes these three points about the disease characteristics and treatments:
In a study reported by Jin Shi and Chen Quanliang (2), the researchers examined 85 patients with hepatitis C and 37 patients with hepatitis B and compared their general symptom profile. The differential categories used were the following five that have been standardized for all kinds of hepatitis since 1992 by the Liver Disease Committee of the Chinese Association for Traditional Chinese Medicine and Pharmacology:
A general comparison showed that hepatitis C patients were generally older and had a history of blood transfusion; hepatitis B patients often had a close relative afflicted with the same disorder. At the same time, symptoms were much less severe in patients with hepatitis C. A comparison of TCM symptom complex showed equal distribution between the two types in relation to liver qi stagnation, yin deficiency, and yang deficiency, but a markedly higher incidence of blood stasis among patients with hepatitis C, and a markedly higher incidence of damp-heat among patients with hepatitis B.
However, these results may not reflect much on the difference between hepatitis B and C disease. Those with hepatitis C tended to have a higher incidence of blood stasis, but were also older: the elderly tend to have blood stasis. Those with hepatitis B tended to have higher incidence of damp-heat, but damp-heat is probably the main manifestation of more severe hepatitis (see below), which was the condition of those in the study with hepatitis B.
In the opinion of the authors of that report, TCM treatment protocols for hepatitis C should focus on the following: 1) clear pathogens and resolve toxins; 2) remove toxins by strengthening the righteous qi; and 3) transform stasis to prevent cancer formation (liver cancer is a major cause of death from chronic hepatitis). These are, in fact, about the same treatment principles as are often applied to hepatitis B.
Comparing hepatitis B and C, Hong Huiwen and his colleagues (3) examined 100 chronic hepatitis B patients and 50 chronic hepatitis C patients. As noted previously, the patients with hepatitis B tend to be younger than those with hepatitis C (32.7 vs. 46.1 years, mean values in this study). These authors thought that hepatitis B tended to be transmitted more with "socializing"--indulgence in illicit injected drugs and unsafe sexual activity, among other things-which not only accounts for the younger age, but also the tendency for it to affect males (in their group, 89 males and 11 females had hepatitis B; in China it is primarily young men who partake in high-risk "socializing"). Getting a blood transfusion due to diseases of old age was thought to be the reason that hepatitis C tended to involve older individuals and have less sexual differentiation in incidence rates (35 males, 15 females in the hepatitis C group). As to the categories of disorder:
|
Hepatitis B |
Hepatitis C |
|
|
Damp-heat |
41% |
26% |
|
Blood stasis |
1% |
12% |
|
Liver and kidney yin deficiency |
15% |
8% |
|
Liver qi stagnation with spleen qi deficiency |
42% |
54% |
|
Spleen and kidney yang deficiency |
1% |
0% |
These findings tend to confirm the previous report, which was that there were similarities in frequency of liver and kidney yin deficiency, liver qi stagnation, and spleen/kidney deficiency between the two groups, but that there was more damp-heat with hepatitis B and more blood stasis with hepatitis C. The authors also presented information on the tongue and pulse qualities. Generally, patients with hepatitis B tended to have a pale or dark tongue and a yellow greasy coating and a fine wiry pulse or a wiry slippery pulse; patients with hepatitis C tended to have a dark or dark purple tongue, with a thin white coating, and a fine wiry pulse. These findings lend further support to the contended differentiation into damp-heat and blood stasis categories for hepatitis B and C, respectively.
Without giving details of treatment, the authors state that of the recipes that were given to patients with hepatitis B, there was a higher proportion of heat-clearing herbs and dampness eliminating herbs, with the following ingredients being dominant: hu-chang, oldenlandia, wild chrysanthemum, dandelion, and coptis. For hepatitis C, heat-clearing and blood-cooling herbs were relied upon, mainly: lonicera, oldenlandia, hu-chang, dictamnus, duchesnia, solanum, and lithospermum. The formulas for hepatitis B tended to have more ingredients than those for hepatitis C. Some therapies relied on astragalus and other qi-tonic herbs. In general, hepatitis-C patients received larger doses of astragalus when that ingredient was included.
In a study reported in the 1998 Journal of Traditional Chinese Medicine (4), 108 patients with hepatitis C were analyzed according to TCM. These patients had not used interferon (or had not had drug treatment for at least 6 months) or Chinese herbs (or had not had herbal treatment for at least 3 months). The proportion of males and females was relatively equal: 65 were male, 43 female, with an age range of 22-71 (average age 55). The high average age of this group, and the relatively more equal distribution among males and females correlates well with the proposal that the main risk factor is blood transfusion rather than "socializing." The patients were then evaluated and assigned into the five categories listed above, revealing:
Those with a diagnosis of damp-heat had highly-elevated liver enzymes, while those in the other diagnostic categories only had moderate elevation. The authors believe that it is likely that the symptoms generated by severe liver inflammation (abdominal bloating, nausea, loss of appetite, yellowing of eyes and skin) fit the damp-heat category. The high incidence of blood-stasis was described by the authors as a possible outcome of the tendency of hepatitis C to cause liver cirrhosis. This condition leads to hardening of the liver (and, sometimes the spleen) and partial blockage of the portal vein. This group had a moderate proportion of cases of spleen/kidney yang deficiency, as might be expected with patients having an average age of 55.
In a study of a treatment of hepatitis C (5), the tongue and pulse manifestation of patients with hepatitis C was reported. The distribution of findings were:
|
Dark violet tongue |
52 |
|
Petechia (red spots) |
24 |
|
Red tongue |
14 |
|
Pale tongue |
10 |
|
Yellow greasy coating |
51 |
|
Thin yellow coating |
28 |
|
White greasy coating |
21 |
|
Fine and wiry pulse |
41 |
|
Wiry pulse |
25 |
|
Soft, rapid, floating pulse |
20 |
|
Fine pulse |
14 |
As this analysis reveals, blood stasis, as indicated by the dark violet tongue, is prevalent, as is damp-heat syndrome indicated by the yellow greasy tongue coating. The more prevalent fine and wiry pulse may suggest liver qi stagnation coupled with qi deficiency syndrome; this pulse often accompanies qi and blood stasis.
Despite the obvious trends, such as blood stasis and damp-heat syndromes, the accumulated data and traditional analysis seem to support the approach of treatment design according to differential diagnosis even if a standard "anti-hepatitis-C" drug, herb, or herbal formula is administered. It may be possible to address the different patterns with acupuncture while addressing the viral disease with a standard herbal protocol, but some means of focusing on the individual pattern is probably of clinical benefit, since there are clearly a range of disease manifestations. Hepatitis B is treated by herbs for the traditional categories of pathological disturbance labeled: toxin; damp-heat; qi and blood stasis; and qi, blood, and yin deficiency. Herbs are also given according to specific manifestation of the disease and underlying constitutional factors. The treatment of hepatitis C is similar to that of hepatitis B, with the differences noted above.
In a report by the Institute for Traditional Medicine (see: Treatment of hepatitis B), important herbs for treating viral hepatitis were described and a formulation was mentioned that was developed by ITM and evaluated in China among in-patients with hepatitis B. The seven herb formula (salvia, ligustrum, curcuma, hu-chang, licorice, schizandra, atractylodes) addresses each of the five categories of concern listed above for hepatitis:
The medical reporting of treatments for hepatitis C in China has a number of flaws. Sometimes, the therapies (the herbal formulas) are not specified or only partially specified. Other times, the outcomes of treatment are unclear. Therefore, one should interpret the reports with some care.
One of the most recent reports of effective therapy (6) describes application of a component of the herb sophora (kushen). This is the alkaloid oxymatrine (see: Sophora). In the report, the purity of the compound used was not described. Oxymatrine is usually isolated from sophora root (either from Sophora flavescens or Sophora subprostrata) along with other alkaloids of similar structure, mainly matrine. It was reported that 200 mg of oxymatrine was present in each 2 ml ampule of injectable liquid, which was given intramuscularly at 600 mg/day. Since placebo controls are not looked upon favorably, the control group was given liver-protecting herbs and vitamins (details not given) taken orally. Patients were randomized into the two different treatment groups. The treatment duration was three months.
According to the report, of the 20 patients receiving oxymatrine injections, 17 completed the trial, and of those 17, 8 had their hepatitis-C RNA (measured by PCR) drop below detection. This is a possible cure, assuming that there isn't some small amount of virus left that will activate later, but it certainly counts as a significant remission. The potential "cure rate" may thus be 8/20 or 40% (as good as the interferon plus Ribavirin results), or as high as 8/17 (assuming the drop-outs had equal chance of good results had they remained in the study), or about 47%. The control group had 23 patients, of which 18 completed the trial, with only 1 having a PCR value drop below detection (cure rate of 1/23 to 1/18 or about 5%). The liver-enzyme assays showed improvements in both the control and the treatment groups (if liver enzyme tests are relied on alone, many treatments may indicate benefit, while the PCR test is a more reliable test of affecting the virus).
The only adverse effect of the oxymatrine treatment was a near universal complaint of pain at the injection site. One patient experienced apparent allergy reaction after four weeks (skin itching), which was treated so that oxymatrine could be continued.
Oxymatrine was selected for study because it had previously been shown to inhibit viruses (including hepatitis B), enhance cellular immune functions, and reduce liver fibrosis. Sophora subprostrata has been an ingredient in many hepatitis B formulas (given orally in decoction form). Sophora-root-extract injection has been used experimentally and clinically for a variety of disorders at least since 1976. Usual dosages are 200-400 mg per day, though up to 800 mg is given by injection in two divided doses. The tablet of sophora extract has also been administered; an example of the dosage used is 1.5 grams each time (presumably about 20% alkaloids, thus 450 mg), three times daily.
Oxymatrine injections are not an option for treatment outside China, as this would require medical application of an unapproved drug. However, oxymatrine is available for oral administration. The Institute for Traditional Medicine has begun clinical use of oral oxymatrine in tablet form (sophora root extract, 20% oxymatrine, 2% matrine, 1 gram per tablet; three tablets per day for 600 mg oral oxymatrine) as an herbal supplement, not a drug therapy.
Another report of particular interest was published in the Chinese Journal of Integrated Traditional and Western Medicine for Liver Diseases (7), and has been previously described by ITM in several articles since 1994. In the study, there were 128 hepatitis C patients treated, including 31 that also had hepatitis B. The treatment given was claimed to produce remission in 55.4% (alleviation of all symptoms, antibody test turning negative, liver enzymes-ALT and AST-normalized), with most other patients showing improvements following a 3 month treatment period. The original translation of the report had the term "cure," as a result of evidence of the antibody test, but with the new information about viral PCR, this term is now seen as inappropriate. Rather, the improvements noted can only be deemed remission.
The basic formula given was:
|
Qing Tui Fang |
|||
|
salvia |
30 g |
[vitalize blood and remove heat] |
|
|
red peony |
30 g |
||
|
crataegus |
15 g |
||
|
moutan |
15 g |
||
|
forsythia |
30 g |
[clean toxin, remove damp-heat] |
|
|
gardenia |
15 g |
||
|
dandelion |
15 g |
||
|
ho-shou-wu |
15 g |
[nourish yin and blood] |
|
|
astragalus |
30 g |
[tonify qi to dispel the pathogen] |
|
|
bupleurum |
10 g |
[regulate qi] |
|
The herbs are decocted and the amount indicated here is taken in two divided doses each day. According to the medical report, the formula can be modified to address specific symptoms by adding additional herbs (e.g., for pain in the liver area, add 15 grams peony and 15 grams curcuma; for loss of appetite, add 10 grams hoelen and 10 grams shen-chu; for abdominal distention, add 10 grams magnolia bark and 10 grams perilla stem).
Note that this formula fits the patterns described above of using a high dose of astragalus (30 grams), vitalizing blood and clearing heat from the blood (salvia, red peony, crataegus, moutan; this making up nearly half the dosage of the prescription), and treating heat, toxin, and dampness (forsythia, gardenia, dandelion). It also contains bupleurum to regulate the qi, and ho-shou-wu to nourish kidney/liver yin, thus addressing all the categories of concern. Subjective and clinically observed improvements included alleviation of: lassitude, poor appetite, abdominal distension, liver pain, and hepatic swelling.
The Institute for Traditional Medicine has been providing this formulation in the form of dried decoctions (hot water extracts of the individual herbs, spray-dried) to patients at its clinic and to practitioners elsewhere for application to their patients. The recommended dosage is 9 grams of dried decoction each time, three times daily (which corresponds, roughly, to about 130 grams of herbs in decoction, compared to the 200 gram dosage mentioned in the Chinese clinical report), though some patients take only 2/3 this dose. Formal reports of the effects of this formula used here have not been obtained, but informal reporting seems to indicate that patients with substantially elevated liver enzymes experience a marked improvement in those measures, while those who have only slightly elevated liver enzymes experience little or no change. Thus far, no reports of PCR dropping below detection have been received (PCR testing is still limited). In a few cases, persons who were experiencing digestive disturbance as part of the hepatitis syndrome reported that the herbal formula exacerbated that symptom (which could then be alleviated by altering the formulation to include more herbs to benefit the stomach/spleen system).
Other studies reported in the Chinese medical literature include these:
|
HBsAg negative: |
12.4% (control group: 1.9%) |
|
|
HBeAg negative: |
76.8% (control group: 19.5%) |
|
|
HBc antibodies negative: |
17.5% (control group: 2%) |
|
|
HBV-DNA negative: |
52.9% (control group: 16.7%) |
|
|
HCV antibodies negative: |
29.4% (control group: 8%) |
It has been said that Chinese medical journals only publish positive results. In the case of hepatitis C treatments, that appears to be the case thus far. However, it is clear that the positive results claimed are within the realm of possibility: viral inhibition measured by PCR tests shows results that are comparable to Western medical treatment, and tests showing antibody conversion or liver enzyme normalization are consistent with reports for hepatitis B that have been emerging from the Orient (mainland China, Taiwan, Hong Kong, and Japan) for several years.
With the exception of the report about oxymatrine, all of the treatments rely on complex mixtures of herbs, with or without added interferon therapy. The dosages of herbs, when described, tend to be high. The formulations vary considerably not only from one research center to the next, but also, in those studies which depict syndrome differentiation, from one patient to the next. As with treatment of many other diseases, the Chinese clinical reports indicate a wide range of herbs selected for treatment, and there are many ingredients that are not mentioned in the clinical reports (as a means of retaining a sort of "patent" on the formulation). Among the ingredients mentioned with some frequency in the above reports are gardenia, forsythia, curcuma, bupleurum, salvia, astragalus, tang-kuei, and various types of peony (white peony, red peony, moutan). Some reports mention, off-handedly, the administration of vitamins, either as an accompaniment to herb therapy or as a part of the control group treatment.
To avoid the extremely-high dosage requirements that often accompany the large decoction formulas, a prescription containing just a few key ingredients might be recommended. The Institute for Traditional Medicine is providing (in addition to Qing Tui Tang) the following prescription in the form of dried decoctions and tablets, intended for the case of more severe viral hepatitis involving both blood stasis and damp-heat (but not those of liver/kidney yin deficiency or spleen/stomach weakness), as described in the Chinese literature:
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Bupleurum/Gardenia Formula |
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bupleurum |
15% |
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peony |
15% (5% each of peony, red peony, moutan) |
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gardenia |
15% |
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forsythia |
15% |
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astragalus |
15% |
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salvia |
15% |
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tang-kuei |
10% |
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This formula is a derivative of the traditional Chaihu Qinggan Tang (bupleurum formula for cleansing the liver; Bupleurum and Rehmannia Combination) of the Ming Dynasty. That formula includes bupleurum, peony, gardenia, forsythia, and tang-kuei as essential ingredients. Astragalus and salvia are important here to address the common problem of blood stasis associated with hepatitis C.
Since herbal teas (either making decoctions, or converting dried decoctions to tea) were utilized in the Chinese clinical trials, a similar form should probably be tried here. Due to the long course of therapy, Westerners may wish to rely on dried extracts (which are swallowed with a glass of water or made into tea) as a more convenient form than the more traditional crude herb decoction. A dose of three teaspoons of dried extracts (about 9 grams), two times daily would be equivalent to a decoction dose of around 100 grams crude herbs daily, the amount intended for the above prescription. A tablet form is in preparation, for which a dose of 8-9 tablets each time, three times daily, is suggested to get this dosage.
Some patients may experience loss of appetite, loose stool or diarrhea, or other reactions in response to treatments with bitter cold herbs, thus one may need to adjust the formulation somewhat if this reaction occurs and persists. An example of adjustment is to remove one or two of the toxin and damp-heat clearing herbs and to instead rely on qi-tonic and dampness-clearing herbs such as those found in Six Major Herbs Combination (Liu Junzi Tang). Another formulation, aside from Salvia/Ligustrum Tablets (mentioned above), is available to address hepatitis: Eclipta Tablets. This formula is suited to those who have liver/kidney yin deficiency complicated by stomach/spleen weakness. Any of these formulas could be taken along with Oxymatrine Tablets. In place of the vitamins given in some of the Chinese clinical trials, ITM has developed two nutritional anti-oxidant preparations that can be utilized: Quercenol (which includes milk thistle extract, several flavonoids, and vitamins C and E) and Alpha Curcumone (which includes alpha-lipoic acid, several antioxidant vitamins, ginseng and curcuma). The dosage is 1 tablet of each, 2-3 times daily, to be taken along with the complex herbal prescription selected for the principal treatment component. These formulas are available by prescription only from practitioners who have access to the ITM literature regarding their ingredients, therapeutic actions, and potential clinical applications.
Until more clinical work with hepatitis C and Chinese herbs is carried out in the United States, it may be difficult to convince medical practitioners and patients to try this method. Because the herbs are non-toxic, some patients may wish to utilize this therapy in place of, or in addition to, treatment by interferon. It is reasonable to begin collecting information from such patients to provide case histories in an effort to eventually develop a well-designed clinical trial.