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1- Ozone and treatment of viral diseases and viral hepatitis

By In مقالات On فبراير 28, 2015


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 Wards

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 <0.001 ) for the SGPT enzyme, and were back to normal in 52 % of cases (P value <0.001) for the SGOT enzyme (normal levels are ≤ 40 U/L) table 1 figure 1– 4.

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. 2 mnth 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

Fig. 1

PCR average number before, during and after ozone therapy

Fig. 2

Number of PCR negative cases during and after ozone therapy

Fig. 3

Normal and abnormal SGOT enzyme levels before and after ozone therapy

Fig. 4

Normal and abnormal SGPT enzyme levels before and after ozone therapy

Fig. 5

Normal and abnormal albumin levels before and after ozone therapy

Fig. 6

Normal and abnormal bilirubin levels before and after ozone therapy

Fig. 7

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.

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