Treatment of Chronic Hepatitis C Virus

An Integrated Approach Using Traditional Chinese Medicine and Acupuncture

James E. Williams

Department of Clinical Medicine, Pacific College of Oriental Medicine, and the Institute for Asian Medicine and Philosophy, San Diego, California

Chronic Hepatitis C Virus (HCV) has emerged as the most important liver disease in the United States and Canada,* with an estimated 4 million Americans infected, and 1% world wide. Currently 8,000 to 10,000 deaths occur each year in the United States alone due to HCV, and without effective intervention that number is expected to triple within 20 years.* Due to the high incidence of viral hepatitis in China, Traditional Chinese Medicine (TCM) has had a long history of treating the chronic hepatitis utilizing a systematic and comprehensive methodology underlying the principles of treatment. The purpose of this paper is to determine if TCM is effective in the management of chronic viral hepatitis C and how alternative and complementary therapies may be used in an integrated treatment plan.

Hepatitis C Virus

Hepatitis C virus (HCV) is a RNA virus of the Flaviviridae family. HCV becomes a chronic condition is 85% of infected individuals. Cirrhosis and hepatocelluar carcinoma are the predominant causes of death in HCV infection. The range of additional complications following HCV infection is broad. Sources of infection include injection drug use, needle-stick accidents by health workers, contact with infected blood products, sexual contact with menstrual blood in infected persons, infants born to infected women, and tattoos.

The process of chronic HCV is insidious, progressing slowly and usually clinically silent without symptoms or physical signs during the first two decades after infection. First symptoms only appear in the majority of cases when advanced liver disease has already developed, although some individuals complain of fatigue, joint pain, and itching during the early course of the disease. Disease progression appears to be more rapid in the elderly and immuno-compromised individuals. Natural immunity to HCV infection appears to be weak or absent.

Although one-third of patients demonstrate normal serum alanine aminotransferase (ALT/SGPT) levels, persistent elevation of ALT for more than six months is the primary laboratory marker for HCV. Antibodies to HCV or circulating viral RNA are present in all cases. Viral count can be estimated by quantitative HCV RNA by PCR (polymerase chain reaction assay).* There is little or no correlation between disease severity or disease progression and ALT levels or HCV RNA titers. Liver biopsy is useful in evaluating the severity of liver damage.

The Liver According to Traditional Chinese Medicine

The main function of the liver is to rule the even flow of qi.* This free flow of qi, intrinsic vital energy, results in four major facets: harmony of the emotions, harmony of digestion, harmony of menstruation, and the secretion of bile. The liver also is considered to store blood, rule over the function of tendons, open into the eyes, and manifest in the nails. Liver dysfunction is divided into several diagnostic types: stagnation and depressive syndromes; deficiency syndromes; and excess syndromes.* The etiology of liver disorders come from several different causes: kidney yin deficiency, emotional stress, dietary indiscretions, and microbial infection.

Diagnostics

Although hepatitis is not specifically mentioned in the Nei Jing, liver and gall bladder damp heat syndrome (gan dan shi re)* most closely resembles the symptom profile of hepatitis in the acute stage. Symptoms include flu-like malaise, fever, dark urine, light colored stools, jaundice, fatigue, anorexia, nausea, and itching. In the chronic stage symptoms include fatigue and malaise, mild fever, liver pain, decreased appetite, and itching skin, and more closely resemble spleen deficiency syndromes complicated by dampness with either heat or cold.

Patients with HCV may have no symptoms in the initial stages and only gradually manifest symptoms well into the chronic stage. A low-grade damp heat syndrome is usually present, complicated by deficiency of qi and yin, stagnation of qi and blood, hyperactive yang, and retention of heat.

Table 1. TCM Diagnostic Categories Related to Chronic Hepatitis*

Stagnation & Depressive Syndromes

Deficiency Syndromes

Excess Syndromes

Disharmony of Liver Qi

(gan qi bu he)

Liver & Gallbladder Qi Deficiency (gan dan qi xu)

Liver & Gallbladder Damp Heat

(gan dan she re)

Liver Stagnation

(gan yu)

Liver Yin Deficiency

(gan yin xu)

Liver Qi Surging Upward

(gan qi shang ni)

Liver Invading Spleen

(gan qi fan pi)

Liver Blood Deficiency

(gan xue xu)

Liver Heat

(gan re)

Liver Stagnation with Spleen Deficiency (gan yu pi xu)

Spleen Qi Decificiency

(pi qi xu)

Liver Fire

(gan huo)

Liver Attacking Stomach

(gan qi fan wei)

 

Liver Yang Excess

(gan yang shang kang)

Blood Stagnation

(yu xue)

 

Liver Fire Flaming Upward

(gan hou shang yan)

 

Integrated Therapy

The therapeutic goals for chronic HCV should include: (1) the relief of symptoms, if present; (2) eradication of the virus if possible; (3) prevention of the progression of end-stage liver disease; (4) enhancement of the natural immune status; and (5) the reduction and prevention of side-effects of conventional therapy. Serious liver disease constitutes a chronic uncontrollable stress resulting in physical, emotional, and immune disruption. Integrated therapy offers the most promise: utilizing conventional methods combined with alternative therapies, life-style modification, and psychological counseling.

 

Western Medicine

Interferon alpha injections and the oral antiviral agent Ribavirin, a nucleoside analog, are the medications of choice. Effectiveness is determined by normalization of ALT and loss of detectable HCV RNA. Meta-analysis has shown that Interferon alpha when given for one year has an effective rate of 16-23%.* Combined therapy, interferon plus Ribavirin, appears to produce a sustained response in 40% of patients. 50% of patients who relapse and are treated with a second course, respond favorably. Obviously, the majority of patients do not respond to therapy and these cases are the most difficult to manage. Liver transplant, a life-saving measure, is reserved for patients with end-stage liver disease, though mild HCV infection to the transplanted liver occurs in most of these patients.

Drug withdrawal and side-effects of therapy are common. The majority of patients experience severe flu-like symptoms (low grade fever, chills, severe malaise and fatigue, headaches, arthralgia and myalgia) due to therapy. Tachycardia, restlessness, irritability, depression, and insomnia may also occur. Bone marrow suppression and severe neuropsychiatric disorders, including suicidal depression, may occur latter in therapy.* Treatment of side-effects is based on symptoms and includes the use of acetaminophen, electrolyte management, and serotonin regulating antidepressants.

Traditional Chinese Medicine

Since the clinical picture for chronic hepatitis is of mixed pathology, excess combined with deficiency, a comprehensive therapeutic strategy is required. Though the primary therapeutic method for the treatment of chronic hepatitis is to drain the liver (xie gan) of excess heat and dampness, the treatment principle should follow a coordinated, balanced approach of clearing damp heat while supporting deficiency conditions, regulating qi and blood, and harmonizing conflicting organ energies, while calming the emotions.*

Due to the high incidence of hepatitis B in China, many herbal formulas have been used for this disease, therefore modern TCM therapy for HCV is based on the model for treating hepatitis B. Most research has been also on hepatitis B, though a recent double-blind study* in Australian utilizing a new Chinese formula, CH-100, for HCV indicated significant reduction in ALT, however without viral clearance.

Minor Bupleurum Decoction (xiao chai hu tang, or sho-saiko-to)* has been one of the most researched formulas for hepatitis in China and Japan, and is commonly used by North American practitioners for all types of liver disorders.* Though researchers are not entirely aware of how this formula works, it is suggested that it may activate macrophages, increase cytokines production, and promote natural killer cell activity.*

Other commonly used formulas include Gentiana Longdancao Decoction to Drain the Liver (long dan xie gan tang) and Artemisia Yinchenhao Decoction (yin chen hao tang). Cohen has reported positive results using a new formula, Ecliptex, containing Herba Ecliptae (han lien tsao).*

Complications or side-effects of these herbs appear rare and usually constitute gastrointestinal upset or diarrhea which are self-limiting upon reduction of dose or discontinuance of medication. There is evidence that Minor Bupleurum Decoction may cause interstitial pneumonitis by over stimulating neutrophil activity leading to peroxide-induced lung damage when used in combination with interferon alpha.*

List 1. Commonly Used Chinese Herbal Formulas with Ingredients for Hepatitis

Gentiana Longdancao Decoction

long dan xie gan tang

 

Radix Gentianae Longdancao (long dan cao)

Radix Scutellariae (huang qin)

Fructus Gardeniae Jasminoidis (zhi zi)

Caulis Mutong (mu tong)

Semen Plantaginis (che qian zi)

Rhizoma Alismatis Orientalis (ze xie)

Radix Bupleurum (chai hu)

Radix Rehmanniae Glutinosae (sheng di huang)

Radix Angelica Sinensis (dang gui)

Radix Glycyrrhizae Uralensis (gan cao)

 

Minor Bupleurum Decoction

xiao chai hu tang (sho-saiko-to)

 

Radix Bupleurum (chai hu)

Radix Scutellariae (huang qin)

Rhizoma Pinelliae Ternatae (ban xia)

Rhizoma Zingiberis Officinalis Recens (sheng jiang)

Radix Ginseng (ren shen)

Honey-fried Radix Glycyrrhizae Uralensis (zhi gan cao)

Fructus Zizyphi Jujubae (da zao)

 

Artemisia Yinchenhao Decoction

yin chen hao tang

 

Herba Artemisiae Yinchenhao (yin chen hao)

Fructus Gardeniae Jasminoidis (zhi zi)

Radix et Rhizoma Rhei (da huang)

 

CH-100

 

Radix Salvia Miltiorrhizae (dan shen)

Sclerotium Poria Cocos (fu ling)

Sclerotium Polyporus Umbellati (zhe ling)

Herba Artemisiae Capillaris (yin chen hao)

Herba Taraxicum Magnolici (pu gong ying)

Radix Paeonia Lactiflorae (bai shao)

Panax Psuedoginseng (san qi)

Radix Bupleurum (chai hu)

Fructus Crataegus (shan zha)

Rhizoma Curcumae Longa (jiang huang)

Blechoma longituba [reference unknown]

Radix Astragalii (huang qi)

Radis Codonopsis (dang shen)

Ramus Loranthus seu Visci (sang ji sheng)

Lycium barabarum [probably Fructus Lycii Chinensis (gou gi zi)]

Radix Glycyrrhiza Uralensis (gan chao)

Polygonum cuspidatum [probably Herba Polygoni Avicularis (bian xu)]

Fructus Zizphyii Jujubae (da zhao)

Gentiana manshurica [probably Radix Gentianae Macrophyllae (qin jiao)]

Acupuncture

Although acupuncture is not a primary therapy for chronic hepatitis, it is useful in treating some of the side-effects of conventional therapy, especially headaches, nausea, and insomnia, and as an adjunct to herbal therapies for its ability to regulate qi and blood. Moxibustion may also be used in cold and deficiency cases.

List 2: Commonly Used Acupuncture Points for Hepatitis

Liver & Gallbladder Damp Heat

LV 2 (xing jian), LV 3 (tai chong), GB 34 (yang ling quan), CV 12 (zhong guan), SP 6 (san yin jiao), BL 18 (gan shu), BL 19 (dan shu)

Liver Qi Stagnation with Abdominal Pain

LV 13 (zhang men), LV 14 (qi men), GB 24 (ri yue), CV 13 (shang guan), CV 14 (ju que)

Spleen Deficiency with Dampness

SP 9 (yin ling quan), SP 15 (da heng), ST 36 (zu san li), BL 20 (pi shu)

Nauseau

PC 6 (nei guan)

Kidney Yin Deficiency

KI 3 (tai xi), BL 23 (shen shu)

Other Treatment Options

A number of alternative therapies have been suggested for the treatment and management of HCV.* These include the elimination of alcohol, lowering hepatic iron concentrations by repeated venesection, use of hydrophilic bile salts, supplemental use of antioxidants (vitamins C and E, and lipoic acid), oral N-acety cysteine (NAC) combined with interferon alpha, aspirin and other nonsteroidal anti-inflammatory drugs, and thymosin with interferon alpha.

Schisandrin C,* derived from the Chinese herb Schisandra chinensis (wu wei zi), and Silymarin, the active flavonoid component of Silybum marianum, have been shown to have liver protective action. Licorice extract,* Glycyrrhiza glabra, has been shown to be effective when combined with interferon alpha.

Case Studies

CASE # 1. Chronic Hepatitis C, Treated with Interferon Alpha and Ribaviron

Chief Complaints & Presenting History: 48 year old Caucasian male diagnosed with HCV in 1993 upon routine screen at a blood bank. There was no history of IV drug use or transfusion. Onset was insidious. His symptoms upon presentation in 1997 were principally side-effects of conventional drug therapy, which included severe fatigue, constant nausea, headache, insomnia, and agitation. He was also anemic with a low RBC and hemoglobin, and low WBC. At the time of presentation he was taking 3 million units of Interferon alpha by injection daily, with 400 mg of Ribavirin 3 times daily. Shortly after he began alternative therapy, his Interferon alpha was changed to Infergen, a newer generation interferon. He was also taking the anti-depressant Paxil. TCM examination revealed a deficient pulse with enlarged pale tongue with a thick yellow coat, and a slightly sallow yellowish complexion. There was abdominal tautness without pain or hepatomegaly.

 

 

Assessment & Impressions: Chronic HCV with side-effects of Interferon alpha and Ribavirin therapy; TCM: Liver and Gallbladder Damp Heat with Excess Liver Yang causing Liver Fire Flaming Upward, and Liver Attacking Stomach complicated by Spleen Qi Deficiency.

Therapeutic Plan:

acupuncture 2 times weekly (LV 2, 3; KI 3; ST 36; PC 6; CV 12, 13)

Minor Bupleurum Decoction, alternating with Gentiana Decoction

N-acetyl cysteine, 500 mg two times daily

live cell extracts of thymus and mesenchyme, oral

multivitamin and mineral; and antioxidant formula with glutathione

zinc, 75 mg daily

selenium, 1200 mcg daily

vitamin C, 1-2 gm 2-3 times daily, depending on tolerance

vitamin E, 1200 IU daily

Phyllantus, Curcumin, and Silymarin extracts, alternating monthly

Echinacea extract, with every other week off

Diet: Avoidance of alcohol, oily and fatty foods, red meats, spicy foods.

Results & Discussion: After two months of therapy, the majority of symptoms were eliminated. After six months the patient discontinued drug therapy for two months, however upon resumption of therapy all symptoms resumed. He returned to my office and was treated two times with acupuncture which helped reduce symptoms. ALT and PCR declined consistently, most likely due to the Interferon and Ribaviron. Acupuncture, TCM, and supportive natural therapeutics effectively controlled side-effects of the drug therapy. Though the liver protective function effects of the treatments remain unknown, a significant reduction in ALT, GGT, and PCR occured within 2 months after initiating alternative therapies.

 

 

 

Table 2. Liver Function Tests and Viral Markers

Dates Laboratory Studies

 

ALT/SGPT (0-45)

GGT (0-65)

PCR Quantitative

HCV Antibody

8/9/93

     

positive

11/22/94

203

     

1/17/95

138

     

4/25/95

199

     

6/19/95

88

     

9/27/95 (started interferon 3 million units 3 times weekly)

65

 

3,142,300

 

1/31/96

31

 

915,600

 

7/26/96

28

 

354,562

 

9/24/96

40

80

   

12/13/96

35

 

124,000

 

1/08/97

20

     

3/17/97

15

   

positive

5/01/97

   

21,630

 

6/30/97

14

     

9/08/97 (acupuncture started)

19

 

145,000

 

11/03/97

16

50

42,000

 

 

CASE # 2. Chronic Hepatitis C, Complicated by Diabetes and Hypertension

Chief Complaints & Presenting History: 50 year old Caucasian male with chronic HCV from IV drug use at least twenty years prior, with the chief complaint of fever of unknown origin diagnosed by an infectious disease specialist. After an episode of bronchitis, he maintained a persistent low-grade fever of 99-100 degrees F, with a tidal presentation worse in the later afternoon. Vital statistics of 58", 290 lbs, BP 150/90. Symptoms included fatigue, joint pain, neuropathy in feet, without sweating or chills. He was also thirsty, with dry throat, dry cough, and reported yellow urine with strong odor. Laboratory markers revealed persistent elevation of ALT, decreased albumin, elevated ALK PHOS, an elevated sedimentation rate, and anemia. The pulse was slippery; the tongue pale, enlarged, with a sticky yellow coat. Complex was dark. The abdomen was enlarged and flaccid without ascites.

Assessment & Impressions: Chronic HCV, fever of unknown origin, non-insulin dependent diabetes, obesity, hypertension; TCM: Liver Gallbladder Damp Heat with Kidney Yin Deficiency, complicated by trapped pathogenic heat and blood stagnation.

Therapeutic Plan: Minor Bupleurum Decoction, with Coptis Decoction to Relieve Toxicity

vitamin C buffered powder, 6-8 gms daily

Results & Clinical Course: Follow-up was performed monthly. There was no change in fever at the end of two months. Rehmania Six Decoction was added and Coptis Decoction removed. Within two weeks of therapy all signs of fever were eliminated. In addition, over the next several months, the glucose normalized to a range of 100-117 and the patient was able to discontinue Micronase. His blood pressure lowered to 140/75, though he continued to take Capotin and Diazide. He was put on long-term treatment with Minor Bupleurum Decoction alternating with Gentiana Decoction, and low dose continual Rehmania Six Decoction. Silymarin extract was added, along with a multivitamin/mineral and an antioxidant formula. Weight loss was strongly encouraged. At the end of one year: the fever had not returned, blood sugar remained normalized, energy had improved significantly; there was no neuropathy and joint pains were milder and rare. He continued to take diuretics and was changed to Lasix. He lost 75 lbs. with improved diet. Patient returned six months later with a recurrence of afternoon fever and joint pain. Regular weekly acupuncture visits were added, (LV 3, GB 34, SP 9, KI 3, CV 12, LV 14, LI 4). After three weeks the fever subsided and eventually disappeared. Patient has maintained bi-weekly appointments for acupuncture since. Laboratory markers revealed improvement in Alkaline Phosphatase, no significant change in ALT, though no worsening, and a normalization of a persistently elevated ESR. RBCs had normalized without other signs of anemia at the end of the first six months of treatment.

 

 

Table 3. Liver Function Tests and Sedimentation Rate

Dates Laboratory Studies

 

ALT/SGPT

(0-45 IU/L)

ALK PHOS

(30-110 U/L)

Albumin

(3.5-5.0 gm/dl)

ESR

(0-20 mm/hr)

1/5/95

(began alternative therapy)

134

113

3.4

 

5/17/95

122

98

3.2

39

8/11/95

186

120

3.2

12

8/20/96

80

58

2.6

 

7/31/97

(began regular acupuncture)

136

73

2.9

35

3/25/98

179

73

3.1

 

10/15/98

162

72

3.2

4

Discussion: This patient had choosen not to take conventional therapy for the HCV, though he had no objection to management of his elevated blood sugar and hypertension with drugs. After nearly three years with alternative methods, his general health improved considerably: evidenced by the weight loss, lowering of blood pressure, and improved glucose control. In addition, symptoms associated with the chronic HCV (joint pain, fatigue, malaise, and low-grade fever) were eliminated and there appeared to be no worsening of liver function markers, with even slight improvement evident, suggesting effective management of the disease. Since no liver biopsy was performed, liver protective results are difficult to evaluate.

Conclusion

Though the ultimate therapeutic goal is the eradication of all detectable virus, in many patients with chronic HCV this outcome is very difficult or impossible to achieve. Because most patients do not experience a sustained response to conventional therapy; that combined therapy has shown the best results to date; and that side-effects to conventional therapy are so severe, an integrated approach to the treatment of chronic HCV seems desirable. Such a therapy would include conventional allopathic methods, dietary restrictions (avoidance of red meat and iron containing vitamin supplements), alcohol avoidance, traditional Chinese herbs, nutritional supplementation, and acupuncture. Therapeutic goals must be modified towards the achievement of useful clinical results, including: (1) the lowering of viral levels; (2) reduction in active liver inflammation; (3) enhancement of natural immune status; (4) non-toxic symptom management; (5) slowing of the rate of progression of hepatic fibrosis; and (6) the prevention of cirrhosis and hepatocellular carcinoma. Additional studies and further research are necessary, however in the interim integrated therapy holds the most promise.

REFERENCES