Ozone Therapy in Patients with viral Hepatitis C

Author M. N. Mawsouf * **
Author T. T. Tanbouli **
Author W. I. El-Tayar **
Author N. El-Masry **
Author W. Anas **
Publication * Cancer Institute, Cairo University
Publication ** Cairo Medical Clinics
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Ozone Therapy in Patients with viral Hepatitis C – A Clinical Study

 

Abstract

Hepatitis “C” is a medical problem in Egypt. The usual line of treatment is very expensive with major side effects and low efficacy especially in type 4, which is common in Egypt. The aim of this study is to evaluate the role of ozone as a safe line of treatment. This study included 50 type 4 hepatitis “C” patients, 44 males and 6 females. Their age ranged between 23 and 58 years. Investigations including C.B.C., liver function tests, A.F.P., serological tests for Bilharziasis, P.C.R. quantitative for H.C.V., prothrombin time and concentration and abdominal ultrasonography were done before and 8 weeks, 24 weeks after treatment with ozone. Patients received combined treatment of Major AutoHaemotherapy in a dose range from 2.8 mg to 8.4 mg and rectal insufflation in a dose range from 6mg to 12 mg per visit. The numbers of visits were three times per week for 12 weeks followed by twice per week for 12 weeks. The general condition in 94 % of cases improved. There was a decrease in the quantitative P.C.R. (viral load) in 71.8 % of cases that reached –ve P.C.R. in 24 % of cases after 8 weeks treatment. The number of -ve P.C.R. cases for HCV virus increased to reach 36 % of cases after 24 weeks treatment. There was a statistically significant improvement as regards the parameters of SGOT, SGPT, albumin, bilirubin and prothrombin after 8 weeks from the start of the study. Ozone therapy was found to be an effective, safe and less expensive method in Hepatitis “C” patients.

Key Words

Hepatitis, Ozone, HCV

Aim of the Study

This study was made to evaluate the effectiveness of ozone therapy in hepatitis C genotype 4 infections and to evaluate a proposed ozone therapy protocol in HCV genotype 4 treatment.

Introduction

Hepatitis C (HCV) is a worldwide medical problem. It is estimated that more than 300 millions on earth are suffering from HCV. Hepatitis C is a major medical problem in Egypt. It is postulated that more than 15% i.e. more than 10 millions of the population in Egypt are suffering from HCV. This disease is slowly progressing, detected mainly accidentally, devitalizing and difficult to treat. The usual line of treatment is very expensive with major side effects and low efficacy [1, 2].

HCV in most cases leads to complications e.g. liver cirrhosis, ascitis, liver carcinoma and ultimately liver cell failure. Liver Cirrhosis is estimated to develop in 20 -25 % of patients with HCV within 20 years. Hepato-cellular carcinoma in 5% of patients.

It is not only a medical problem, but also an economic problem (less work, less production and very high costs of usual treatment). So far there are six genotypes of HCV with worldwide prevalence of genotypes 1, 2 &3. In Africa genotype 4 and 5 are more dominant. In Asia genotype 6 is more dominant. Genotype differences have shown varying susceptibility to antiviral therapy. In Egypt genotype 4 is prevalent and it is known that is relatively resistant to antiviral treatment [3]. The main line of treatment nowadays for hepatitis C includes interferon and ribavirin. Ribavirin and interferon have significant medical and psychiatric side effects [1].

Antiviral effect of ozone

Ozone is a powerful oxidizing agent. It disrupts viral envelope proteins, lipoproteins, lipids, and glycoproteins. The presence of numerous double bonds in these unsaturated molecules makes them vulnerable to the oxidizing effects of ozone. Molecular architecture is disrupted and widespread breakage of the envelope ensues. Deprived of an envelope, virions cannot sustain nor replicate themselves. Ozone proper, and the peroxide compounds it creates, may directly alter structures on the viral envelope, which are necessary for attachment to host cells. Peplomers, the viral glycoproteins protuberances that connect to host cell receptors are likely sites of ozone action. Alteration in peplomer integrity impairs attachment to host cellular membranes foiling viral attachment and penetration [4 -12].

Ozone stimulate leucocytes function and cytokine production
Ozone is a powerful oxidant by itself and leads to production of peroxides with an oxidative power. H2O2 crosses the cell membrane and activates the cytoplasmic gene-regulatory nuclear factor kappa B, ultimately causing the transcription of mRNAs of several cytokines, namely interleukin (IL-1,2,4,6,8,10), tumor necrosis factor (TNF-µ) and interferon (IFN b and g) [13, 22].

In HCV, viral load appears to be a major factor in the invasiveness and virulence of the disease process. Ozone induces the release of cytokines by leucocytes. Stimulation of the immune mechanisms will lead to significant reduction of circulating virions [14 – 22].

Patients and methods

This study included 50 type 4 hepatitis “C” patients, 44 males and 6 females. Their age ranged between 23 and 58 years. Investigations including C.B.C., liver function tests, A.F.P., serological tests for Bilharziasis, P.C.R. quantitative for H.C.V., prothrombin time and concentration and abdominal ultrasonography were done before and 8 weeks, 24 weeks after starting treatment with ozone. Patients received combined treatment of Major AutoHaemotherapy in a dose range from 2.8 mg to 8.4 mg and rectal insufflation in a dose range from 6 mg to 12 mg per visit. The numbers of visits were three times per week for twelve weeks followed by twice per week for another twelve weeks. Investigations were repeated after 8 and 24 weeks of treatment. General health and daily activity were observed.

Ozone Treatment Protocol

First session of major AutoHaemotherapy was given in a concentration of 20 µ/ml ozone in oxygen for two successive times, then increased to 25 µ/ml ozone in oxygen for another two successive times and so on, increasing the concentration by 5µ/ml every two sessions till reaching a maximum of 60µ/ml were this concentration was fixed till the end of treatment course. The rationale of start low and go slow was respected. The ozone in oxygen volume was fixed in all sessions at 140 ml. The blood weight was constant in each session at 140 gm.

First session of rectal insufflation was given in a concentration of 15 µ/ml ozone in oxygen with a volume of 250 ml for two successive times, then increased to 20 µ/ml ozone in oxygen with the same volume for another two successive times, then 25 µ/ml x 250 ml twice, then 30 µ/ml x 250 ml twice followed by 30 µ/ml x 300 ml, then 35µ/ml x 300 ml twice till we reach a maximum of 40µ/ml x 300 ml were this concentration and volume was fixed till the end of treatment.

Results

It was found that following eight weeks of ozone therapy, the viral load decreased in 63.85% of cases (P value < 0.004) that reached zero reading in 24 % 0f cases (P value <0.001). Following 24 weeks of ozone therapy, there was further decrease of the viral load that reached 71.84% of cases (P value < 0.005) with a zero reading in 36 % 0f cases (P value <0.001). After eight weeks of ozone therapy, the abnormal enzyme levels were back to normal in 58 % of cases ( P value After eight weeks of ozone therapy, the abnormal bilirubin levels (normal value ≤ 1 mg%) were back to normal in 28% of cases (P value < 0.001). Following also the same period of therapy, the abnormal albumin parameters (normal value ≥ 3.5 mg %) were back to normal in 18% of cases (P value < 0.032). The prothrombin concentration improved towards the normal level (P value < 0.001) table 2 figure 5-7.

 

Table 1

Number

Sex

PCR

PCR 2mnth

PCR 6 mnth

SGOT

SGOT2mnth

SGPT

SGPT2mnth

1

Male

5540000

3035000

5750000

39

37

75

12

2

Male

200000

0

0

70

35

65

33

3

Male

91000

31000

12000

80

21

76

22

4

Male

10000000

7003000

3400000

46

33

50

32

5

Male

199010

11000

3500

90

46

50

46

6

Male

2030000

700000

27000

78

33

65

22

7

Male

100000

0

0

69

24

75

17

8

Male

164000

54000

0

38

22

30

25

9

Male

89000

43000

15000

62

40

61

23

10

Male

12000000

5000000

3400000

123

88

232

85

11

Male

1200000

0

0

138

27

112

33

12

Male

1300000

22000

2800

80

36

60

39

13

Male

650000

4500

0

138

71

314

31

14

Female

1115000

3000

1200

24

14

24

17

15

Male

3400000

810000

53000

38

35

23

21

16

Female

954618

1500

0

156

44

163

45

17

Male

1500

0

0

60

33

59

31

18

Male

550000

240000

84000

34

40

50

32

19

Female

500000

1300

0

76

50

85

44

20

Male

103000

36000

5100

80

15

60

13

21

Female

1300000

58000

36000

95

30

85

24

22

Male

1200000

720000

53000

54

40

61

29

23

Male

320000

61000

24000

96

40

80

33

24

Male

586000

119000

82000

44

38

30

39

25

Female

260000

117000

29000

67

36

40

20

26

Male

29223496

10920000

7680000

84

44

120

43

27

Female

10000

0

0

22

21

28

31

28

Male

980000

95000

35000

52

21

17

24

29

Male

240000

180000

0

33

30

42

28

30

Male

1500000

350000

150000

78

65

42

41

31

Male

120000

90000

50000

31

29

34

22

32

Male

300000

100000

5000

78

46

61

29

33

Male

1352000

0

0

65

33

59

39

34

Male

389000

140000

39000

68

49

107

57

35

Male

29605

0

0

50

37

107

43

36

Male

92000

0

0

43

28

53

22

37

Male

120000

65000

11000

147

30

89

30

38

Male

822000

0

0

92

42

92

30

39

Male

157000

68000

40000

70

35

73

28

40

Male

1000000

500000

320000

55

33

59

32

41

Male

470000

210000

36000

63

45

83

33

42

Male

690000

45000

75000

62

31

59

30

43

Male

550000

0

0

143

43

105

45

44

Male

210000

120000

49000

56

26

41

37

45

Male

2250000

5000

0

98

37

75

34

46

Male

112000

0

0

30

31

45

22

47

Male

8756307

2742000

168000

72

29

32

26

48

Male

27000

0

0

28

24

18

20

49

Male

288000

90000

36000

60

110

54

99

50

Male

160000

67000

25000

65

45

60

46


Table 2

Number

Bil.

Bil. 2 mnth

Alb.

Alb. 2 mnth

Prothro.%

Prothro.% 2 mnth

HB %

HB 2 mnth

1

0.9

0.9

3.9

4.0

90

91

13.5

13.8

2

0.8

0.8

3.2

3.9

77

86

12.2

14.1

3

2.3

1.3

4.3

4.3

96

96

15.2

15.6

4

1.0

0.9

4.1

4.2

80

82

15.1

15.2

5

0.8

0.8

3.9

4.1

85

99

13.9

14.0

6

1.1

1.2

3.3

3.5

80

86

14.2

14.3

7

0.8

0.7

4.6

4.7

70

76

15.5

16.7

8

0.7

0.8

3.9

4.2

72

84

13.5

14.3

9

0.6

0.7

4.2

4.3

86

92

15.8

16.1

10

1.1

0.7

4.1

4.5

82

100

12.0

13.1

11

2.0

1.1

4.2

4.4

89

90

13.0

13.2

12

1.2

1.1

3.9

3.6

90

91

15.1

15.1

13

2.1

0.8

2.8

4.7

85

100

12.7

12.9

14

0.7

0.8

3.9

0.4

75

80

11.9

12.1

15

0.8

0.8

4.8

4.9

100

100

14.8

15.0

16

1.1

1.0

3.4

3.8

80

90

13.6

14.0

17

1.2

0.8

4.1

4.3

92

100

14.0

14.2

18

0.9

0.8

3.8

3.9

40

76

14.2

14.4

19

1.4

1.2

2.8

3.1

60

68

11.6

12.0

20

0.7

0.7

4.1

4.3

88

89

13.9

14.0

21

3.3

2.0

2.8

3.0

64

70

10.0

11.0

22

1.0

0.9

3.7

3.8

77

87

13.1

14.5

23

0.6

0.6

4.0

4.4

79

80

13.2

13.9

24

1.0

0.6

4.7

4.6

82

96

13.6

13.1

25

1.2

0.8

3.2

4.3

65

87

11.2

13.5

26

0.5

0.6

3.9

4.0

80

86

15.0

16.3

27

0.8

0.7

3.8

3.9

100

100

12.9

12.8

28

1.2

0.9

3.2

4.0

68

98

14.0

14.1

29

1.2

0.8

3.5

3.5

83

89

12.7

12.9

30

1.7

1.1

3.9

4.2

71

80

13.6

14.2

31

0.6

0.7

3.8

4.2

100

100

13.9

14.5

32

1.6

1.1

2.7

3.3

56

82

14.2

14.7

33

0.5

0.6

3.9

4.1

75

86

13.6

14.9

34

1.7

0.8

3.6

3.5

82

87

13.9

15.2

35

1.8

1.2

3.9

3.9

88

90

13.1

13.3

36

0.9

0.9

3.2

3.2

92

96

13.5

14.1

37

1.2

0.8

3.3

3.8

56

86

13.2

14.1

38

1.1

0.7

3.3

3.9

68

85

12.3

13.8

39

1.2

0.7

3.7

3.8

92

100

12.8

13.6

40

1.2

1.1

4.1

4.3

86

85

14.2

14.3

41

1.0

0.8

4.1

4.3

94

100

13.4

14.8

42

0.7

0.8

3.9

3.4

79

84

14.4

11.9

43

1.2

1.0

3.9

4.2

85

90

12.8

13.9

44

1.6

1.2

2.1

2.7

52

72

12.3

13.0

45

1.9

0.8

3.2

3.8

75

89

12.5

13.0

46

0.9

0.8

4.2

4.5

97

100

14.2

14.3

47

0.7

0.4

3.4

3.5

90

90

13.9

14.1

48

0.7

0.7

3.7

4.1

93

100

13.5

14.2

49

1.3

0.9

2.8

3.6

67

75

13.4

15.2

50

0.8

0.9

4.2

4.2

90

91

14.1

14.4

Figure 1

Ozone Therapy in Patients with Viral Hepatitis C

PCR average number before, during and after ozone therapy

Figure 2

Ozone Therapy in Patients with Viral Hepatitis C

Number of PCR negative cases during and after ozone therapy

Figure 3

Ozone Therapy in Patients with Viral Hepatitis C

Normal and abnormal SGOT enzyme levels before and after ozone therapy

Figure 4

Ozone Therapy in Patients with Viral Hepatitis C

Normal and abnormal SGPT enzyme levels before and after ozone therapy

Figure 5

Ozone Therapy in Patients with Viral Hepatitis C

Normal and abnormal albumin levels before and after ozone therapy

Figure 6

Ozone Therapy in Patients with Viral Hepatitis C

Normal and abnormal bilirubin levels before and after ozone therapy

Figure 7

Ozone Therapy in Patients with Viral Hepatitis C

Normal and abnormal prothrombin levels before and after ozone therapy

Discussion

The significant decrease in viral load is an important factor – among other factors – for judging the improvement of a case of hepatitis C virus. In this study, it was found that following ozone therapy; there was a significant reduction of viral load. This decrease was evident after 8 weeks and further decline following another 16 weeks of ozone therapy.

Normal enzyme levels are a very important indicator denoting the sound integrity of liver cells. In this study, it was found that following ozone therapy; there was a significant change of abnormal enzyme levels towards normal values. Some patients received DDB pills that are a Chinese herbal medicine capable of lowering the enzyme level, but without any anti-viral action. Stoppage of DDB will be followed by increase in enzyme level to the previous level. This can explain why some of the patients had a normal enzyme level before starting ozone therapy.

One of the major important parameters that signify liver function are the bilirubin and albumin levels. In this study it was found that both parameters were improved and back to normal with a statistically significant readings denoting liver function improvement.

Clinical observations and questioning of the patients revealed that in 94 % of cases the general condition improved and some of patients returned to work after they were staying at home. Moreover in most cases there were improvement of the quality of life and they had the sense of well-being. All these data points to the important role of ozone a safe, effective method of therapy.

It is understandable that the response to treatment will be less in complicated cases with e.g. liver cirrhosis and ascitis or cases associated with chronic diseases e.g. diabetes and bilharziasis, but however, these were not considered as factors in ineffectiveness.

In this study there was no control group and the patient was considered a control to himself and the main issue, as a clinical study was to compare the clinical and laboratory findings before and after ozone therapy for each patient. In order to reach a proper protocol for ozone therapy, several pilot studies had to be accomplished. Trial MAH twice/week for 2 months, MAH three times/week for 2 months, RI twice/week for 2 months, RI three times /week for 2 months following rationale of start low and go slow. Good results were obtained but not as good as the protocol of this study. Combination of MAH and RI was important the deliver ozone therapy to both systemic and portal circulation. Ozone therapy was found to induce hyper-oxygenation of portal circulation.

Conclusion

As a preliminary study Ozone therapy was found to be an effective, safe and less expensive method in Hepatitis “C” patients but further studies are important. The protocol of ozone therapy in this study was found to be the best of many other protocols dealing with hepatitis C type 4.

References

1.    Dieperink E, Willenbring M, Ho SB. Neuropsychiatric symptoms associated with hepatitis and interferon alpha: A review. Am J Psychiatry, 157(6):867-876, 2000.

2.    Mawsouf MN, Tanbouli TT and Eltayar WI Ozontherapie bei chronischer Hepatitis C, eine klinische studie. Ozono-Handbuch Grundlagen Pravention Therapie. Viebahn-Hansler . Knoch. Mitherausgeber bis 2001.

3.    Maertens G, Stuyver L. Genotypes and genetic variation of hepatitis C virus. In: The Molecular Medicine of Viral Hepatitis. John Wiley & Sons Ltd., London, 225-227, 1997.

4.    Sunnen GV. Ozone in Medicine. Journal of Advancement in Medicine. 1(3): 159-174, 1988.

5.    Bartenschlager R. Candidate targets for hepatitis C virus-specific antiviral therapy. Intervirology, 40:378-393, 1997.

6.    Bolton DC, Zee YC, Osebold JW. The biological effects of ozone on representative members of five groups of animal viruses. Environmental Research , 27:476-48, 1982.

7.    Carpendale MT, Freeberg JK. Ozone inactivates HIV at noncytotoxic concentrations. Antiviral Research, 16:281-292, 1991.

8.    Harrison TJ, Zuckerman AJ (Eds). The Molecular Medicine of Viral Hepatitis. Molecular Medical Science Series. John Wiley & Sons, New York, 1997.

9.    Konrad H. Ozone therapy for viral diseases. In: Proceedings 10th Ozone World Congress 19-21 Mar 1991, Monaco. Zurich: International Ozone Association , 75-83, 1991.

10.    Major ME, Feinstone SM. The molecular virology of hepatitis C. Hepatology, 25: 1527-1538, 1997.

11.    Monjardino J. Molecular Biology of Hepatitis Viruses, Imperial College Press, London, 1998

12.    Wells KH, Latino J, Gavalchin J, Poiesz BJ. Inactivation of human immunodeficiency virus Type 1 by ozone in vitro. Blood, 78(7):1882-1890, 1991.

13.    Paulesu L, Luzzi L, Bocci V. Studies on the biological effects of ozone: Induction of tumor necrosis factor (TNF-alpha) on human leucocytes. Lymphokine Cytokine Research , 5:409-412, 1991.

14.    Bocci V, Luzzi E, Corradeschi F, Paulesu, et al. Studies on the biological effects of ozone: 5. Evaluation of immunological parameters and tolerability in normal volunteers receiving ambulatory autohaemotherapy. Biotherapy, 7:83-90, 1994.

15.    Bocci V. Ozonation of blood for the therapy of viral diseases and immunodeficiencies. A hypothesis. Medical Hypotheses, 39(1):30-34, 1992.

16.    Viebahn R. The Use of Ozone in Medicine. 4th English edition, Haug, Heildelberg, 126-9, 2002.

17.    Bocci V, Luzzi E, Corradeschi F, Paulesu L., Di. Stefano A.. Studies on the biological effects of ozone: 3. An attempt to define conditions for optimal induction of cytokines. LymphokineEvaluati Cytokine Res., 12: 121-6, 1993.

18.    Bocci V, and Paulesu L. Studies on the biological effects of ozone. Induction of interferon g

19.    on human leukocytes. Haematologica, 75: 510-5, 1990.

20.    Bocci V. Ozonization of blood for the therapy of viral diseases and immunodeficiences. A hypothesis. Medical Hypotheses, 39: 30-4, 1992.

21.     Antonelli G., Blalock J.E., Dianzani F. Generation of a soluble IFN-γ inducer by oxidation of galactose residues on macrophages. Cell Immunol, 94: 440-6, 1985.

22.    De Groote D. et al. Direct stimulation of Cytokines (IL-1β, TNF-α, IL-6, IL-2, IFN-g and GM-CSF) in whole blood. I. Comparison with isolated PBMC stimulation. Cytokine, 4:239-48, 1992.