Studies with Liv.52 in the Treatment of Infective Hepatitis, Chronic Active Hepatitis and Cirrhosis of the Liver
Prof. Mandal, J.N., M.B. (Cal.), D.C.H. (Lond.), F.R.C.P. (Edin.), Professor - Director
and Roy, B.K., M.D. (Cal.), Senior House Physician to Professor-Director, Department of Medicine, Medical College and Hospital, Calcutta, India.
Liv.52 in chronic active hepatitis and cirrhosis
Histopathological studies were not undertaken in this category of cases.
All in all, the use of Liv.52 in cases of Infective Hepatitis in our study have shown significant advantages over other conventional therapies in ensuring an earlier all round clinical and biochemical improvement, and these findings compare well with the findings of other workers, and in the absence of a “Specific”, or for that matter even a better drug at the present moment, the preparation Liv.52 can safely be recommended for use in cases of Infective Hepatitis, specially in consideration of its being absolutely free from any side effects.
(2) Chronic Active Hepatitis: The syndrome of Chronic Active Hepatitis is usually a progressive condition, the aetiology of which may be diverse but mostly leading to a common denominator, viz., immunological disturbances affecting the organ. The condition may have a diverse symptomatology as listed in the text of this paper earlier, biochemical evidences of gross liver dysfunction and often pathognomonic histopathological changes in the liver biopsy material.
The overall result of treatment by conventional therapy is usually unsatisfactory, the condition ultimately leading to Cirrhosis of the Liver or early hepatic failure. The situation being so, it was decided to treat 24 patients of Chronic Active Hepatitis with Liv.52 and study its efficacy in the condition. Earlier Das Gupta and Mukherjee (1971)7 reported the results of treatment in 7 cases with this drug, keeping another 3 cases as Controls. They reported good clinical response with marked improvement in Liver Function Tests done at the end of one and a half to two year. Histopathological evidence of improvement of piecemeal necrosis and arrest of progress of lobular distortion were also reported in their cases. Overall, all the Liv.52 treated cases were reported as "improved” with in 1½ to 2 years, while the 3 control cases expired within one year. The present study more or less corroborates the findings of the above workers as will be evidenced by:
(a) Clinical improvement: in 87.5% cases within one year as against 50% in the Control Group. Das Gupta and Mukherjee, noted clinical improvement in all the 7 cases within 1½ to 2 years.
(b) Biochemical improvement: in Liver Function Tests, viz., Serum bilirubin, Serum Alkaline phosphatase, Serum Total protein/Al: Gl, SGOT, SGPT, BSP excretion studies–all showed early improvement in 6 months to 12 months’ time in 87.5% of cases which compares well with the results obtained by Das Gupta and Mukherjee who found improvement in these parameters in all their cases.
(c) Protein Electrophoresis: Quantitative immunoglobulin determination revealed elevation of all types with marked increase in IgG which came down to normal or almost normal within 12 months in 87.5% of the Liv.52-treated cases, and this finding tallies well with those of the above workers.
(d) Histopathological study: Das Gupta and Mukherjee observed disappearance or clearing of piecemeal necrosis of liver cells, evidence of hepatic cell regeneration and arrest of progressive hepatic architectural distortion within 1½ to 2 years in all their 7 cases. In the present study, a comparable result was obtained in 87.5% of cases treated with the drug.
Though the long-term prognosis is considered to be bad in most of the cases, the overall results in the Liv.52 Group were “Fair” to “Good” at the end of 3 years. Cook et al (1970)13 reported good response in 22 out of 49 patients treated with steroids for 3 to 6 years. None of the patients in the present study received steroids, and the overall results appear nearly similar or even better than what was obtained with long-term steroid therapy without the hazards of the latter being involved. It appears worthwhile to plan a regime of combined Liv.52 + steroids therapy in this condition in a representative series of case to see whether the combination will further improve the long-term prognosis.
(3) Cirrhosis of the Liver: Though the aetiology of Cirrhosis of the liver is multifactorial, the net result of the liver injury and the ultimate clinical course of the disease are by and large similar, having a more or less progressively downhill course over a prolonged period. The conventional therapy is often unsatisfactory, and is usually only helpful for some degree of palliation. The present study shows that prolonged treatment of cases of Cirrhosis of the Liver using a comparatively high dose of the drug, Liv.52 (4 tab. t.i.d.), not only produces a better and earlier palliation of the symptomatology, but there is also marked improvement in the biochemical profile as revealed by periodical Liver Function Tests. There was also good evidence to show that, the drug helps regeneration of the hepatic cells and controls the cirrhotic process thus giving a more useful and prolonged life to the unfortunate sufferers from the disease. Only a very long-term follow-up will show whether the disease can be completely “cured” by the drug. The observations of Gupta et al. (1972)4,5 and Mukherjee and Das Gupta (1971)8 are also similar and compare well with the results of the present study. Mukherjee and Das Gupta also stressed the need to continue the therapy with the drug for a minimum period of 9 months for obtaining good results.
Some of the results of the present study may now be highlighted.
(a) Clinical: Improvement of symptomatology was observed in 12-24 months in 73.68% of the cases treated with the drug as against 50% in the Control Group.
(b) Liver Function Tests:
(i) Serum bilirubin, serum Alkaline phosphatase, serum Total protein/Al: Gl, SGOT and SGPT all reverted to normal or near normal in 73.68% of the Liv.52 treated cases within 12-24 months as against only 37.5% of cases of the Control Group within the same period.
(ii) B.S.P. Excretion studies done in a limited number of cases (5 Liv.52 and 5 Control) showed a much greater excretion in 4 out of 5 of the Liv.52 treated cases as against only 1 out of 5 of the Control cases.
Mukherjee and Das Gupta also reported a highly significant improvement in all the above parameters when the cases were treated with the drug for a minimum period of 9 months.
(iii) Protein Electrophoresis showed an increase in all the fractions of globulin in cirrhosis in all the cases with predominance of IgG, which came down to normal within 18-24 months in 73.68% of the cases of the Liv.52 Group against none in the Control Group, 5 of the 8 latter cases showing a further progressive increase in the component within the same period.
(c) Histopathological Studies: Four cases of the Liv.52 Group (as against none in the Control Group) showed a remarkable improvement in 12 months showing a normal liver architecture with minimal fibrosis, and remained so after another 24 months. Another 10 cases showed a fair degree of improvement in liver architecture with arrest of the progress of fibrosis, as against progressive fibrosis and further distortion of the liver architecture in most of the cases of the Control Group.
Mukherjee and Das Gupta, and others also reported more or less similar findings after prolonged treatment of their cases with Liv.52.
Considering the clinical, biochemical and histopathological parameters, the present study revealed “Fair to Good” results in 73.68% of the cases treated with Liv.52 as against only 37.5% of the cases in the Control Group.
A series of long-term experimental studies carried out by different workers substantiate the protective and regenerative action of Liv.52 on the liver against a battery of hepatotoxins (Murkibhavi and Sheth, 195714, Sheth et al, 196015, Joglekar et al16, Patel et al17, Karandikar et al18, 1963, Qazi, 196519, Captain and Syed,20 (1966); Joglekar and Leevy, 197021. Clinically also the drug has been tried extensively by different workers in various liver disorders and allied conditions, and by using different parameters of Liver Function Tests for assessment, as also by studying histopathological changes by serial liver biopsies. These workers have consistently confirmed that Liv.52 accelerates the clinical and biochemical recovery and also improves/arrests the progress of the histopathological changes (vide list of references). The present study adds strong support to and corroborates the findings of earlier workers. It may be said with confidence that in the absence of the availability of any better drug for the treatment of various liver disorders at the present moment, Liv.52 stands out on its own merit as a highly useful adjunct to the present-day therapeutic armamentarium against the ravages of the unfortunate diseases affecting the human liver.
SUMMARY AND CONCLUSIONS
A controlled study was undertaken to observe the efficacy of an indigenous drug Liv.52 introduced and marketed by The Himalaya Drug Co., Bombay on liver diseases. The present study covered a total of 104 cases of which 73 were treated with the above drug, 31 serving as Controls and belonged to the categories given below:
The parameters chosen for assessment and analysis of the cases after follow-up of up to 3 years were (i) Clinical improvement, (ii) Improvement in the Biochemical profile, specially Liver Function Tests and (iii) Histopathological improvement (in the second and third categories).
On analysis of the data obtained after the full study, the results were graded as “Good”, “Fair” and “Poor” according to criteria already indicated in the text.
The following observations and conclusions were then arrived at:
Category (1) Infective Hepatitis: The results of treatment with Liv.52 were considered “Good” in 73.33%, “Fair” 23.33% and “Poor” in 3.33% of cases as against 26.66%, 66.66% and 6.66% respectively in the Control Group, both groups being analysed by the above parameters excepting histopathological studies which were not undertaken in this category of cases.
Category (2) Chronic Active Hepatitis: The results with Liv.52 were considered “Good” in 37.50%, “Fair” in 50.00% and “Poor” in 12.50% of cases as against 0%, 50% and 50% respectively in the Control Group analysed on the basis of all the three parameters.
Category (3) Cirrhosis of the Liver: The results with Liv.52 were considered as “Good” in 21.05% “Fair” in 52.63% and “Poor” in 26.32% of cases as against 0%, 37.5% and 62.5% respectively analysed by all the parameters of study.
No deleterious side effects were noted in any of the cases treated with the drug, even in those who failed to improve and in this respect the drug was considered absolutely safe.
In conclusion, it may be said with some confidence that since the studied categories of liver diseases which are so common in our country producing a significant degree of morbidity and mortality there being no “Specific” treatment for the conditions, the results of treatment with the indigenous drug Liv.52 appear highly encouraging, at least as a good palliative if not curative, to give the unfortunate sufferers an early improvement and a more prolonged, active and useful life. The drug may be considered as a significant advance, at least by one step, towards successful therapy of these chronic liver diseases.
ACKNOWLEDGEMENTS
We are grateful to the Principal-Superintendent, Medical College and Hospitals, Calcutta for kindly giving us permission to undertake the study and trials in the Medical College and Hospitals, Calcutta. Our sincere thanks also go to the teachers of the Department of medicine, M.C.H. who very graciously allowed us to include some of their cases in our study. We are also sincerely thankful to the Heads of the Biochemistry and Pathology Departments of the College for kindly helping us with the relevant investigations in their respective Departments. The supply of drugs was undertaken by The Himalaya Drug Co. without whose generous help the study would not have been possible, and our sincere thanks go to them. And last but not the least, we are immensely thankful to the patients who showed extreme co-operation and forbearance during the whole period of study.
All in all, the use of Liv.52 in cases of Infective Hepatitis in our study have shown significant advantages over other conventional therapies in ensuring an earlier all round clinical and biochemical improvement, and these findings compare well with the findings of other workers, and in the absence of a “Specific”, or for that matter even a better drug at the present moment, the preparation Liv.52 can safely be recommended for use in cases of Infective Hepatitis, specially in consideration of its being absolutely free from any side effects.
(2) Chronic Active Hepatitis: The syndrome of Chronic Active Hepatitis is usually a progressive condition, the aetiology of which may be diverse but mostly leading to a common denominator, viz., immunological disturbances affecting the organ. The condition may have a diverse symptomatology as listed in the text of this paper earlier, biochemical evidences of gross liver dysfunction and often pathognomonic histopathological changes in the liver biopsy material.
The overall result of treatment by conventional therapy is usually unsatisfactory, the condition ultimately leading to Cirrhosis of the Liver or early hepatic failure. The situation being so, it was decided to treat 24 patients of Chronic Active Hepatitis with Liv.52 and study its efficacy in the condition. Earlier Das Gupta and Mukherjee (1971)7 reported the results of treatment in 7 cases with this drug, keeping another 3 cases as Controls. They reported good clinical response with marked improvement in Liver Function Tests done at the end of one and a half to two year. Histopathological evidence of improvement of piecemeal necrosis and arrest of progress of lobular distortion were also reported in their cases. Overall, all the Liv.52 treated cases were reported as "improved” with in 1½ to 2 years, while the 3 control cases expired within one year. The present study more or less corroborates the findings of the above workers as will be evidenced by:
(a) Clinical improvement: in 87.5% cases within one year as against 50% in the Control Group. Das Gupta and Mukherjee, noted clinical improvement in all the 7 cases within 1½ to 2 years.
(b) Biochemical improvement: in Liver Function Tests, viz., Serum bilirubin, Serum Alkaline phosphatase, Serum Total protein/Al: Gl, SGOT, SGPT, BSP excretion studies–all showed early improvement in 6 months to 12 months’ time in 87.5% of cases which compares well with the results obtained by Das Gupta and Mukherjee who found improvement in these parameters in all their cases.
(c) Protein Electrophoresis: Quantitative immunoglobulin determination revealed elevation of all types with marked increase in IgG which came down to normal or almost normal within 12 months in 87.5% of the Liv.52-treated cases, and this finding tallies well with those of the above workers.
(d) Histopathological study: Das Gupta and Mukherjee observed disappearance or clearing of piecemeal necrosis of liver cells, evidence of hepatic cell regeneration and arrest of progressive hepatic architectural distortion within 1½ to 2 years in all their 7 cases. In the present study, a comparable result was obtained in 87.5% of cases treated with the drug.
Though the long-term prognosis is considered to be bad in most of the cases, the overall results in the Liv.52 Group were “Fair” to “Good” at the end of 3 years. Cook et al (1970)13 reported good response in 22 out of 49 patients treated with steroids for 3 to 6 years. None of the patients in the present study received steroids, and the overall results appear nearly similar or even better than what was obtained with long-term steroid therapy without the hazards of the latter being involved. It appears worthwhile to plan a regime of combined Liv.52 + steroids therapy in this condition in a representative series of case to see whether the combination will further improve the long-term prognosis.
(3) Cirrhosis of the Liver: Though the aetiology of Cirrhosis of the liver is multifactorial, the net result of the liver injury and the ultimate clinical course of the disease are by and large similar, having a more or less progressively downhill course over a prolonged period. The conventional therapy is often unsatisfactory, and is usually only helpful for some degree of palliation. The present study shows that prolonged treatment of cases of Cirrhosis of the Liver using a comparatively high dose of the drug, Liv.52 (4 tab. t.i.d.), not only produces a better and earlier palliation of the symptomatology, but there is also marked improvement in the biochemical profile as revealed by periodical Liver Function Tests. There was also good evidence to show that, the drug helps regeneration of the hepatic cells and controls the cirrhotic process thus giving a more useful and prolonged life to the unfortunate sufferers from the disease. Only a very long-term follow-up will show whether the disease can be completely “cured” by the drug. The observations of Gupta et al. (1972)4,5 and Mukherjee and Das Gupta (1971)8 are also similar and compare well with the results of the present study. Mukherjee and Das Gupta also stressed the need to continue the therapy with the drug for a minimum period of 9 months for obtaining good results.
Some of the results of the present study may now be highlighted.
(a) Clinical: Improvement of symptomatology was observed in 12-24 months in 73.68% of the cases treated with the drug as against 50% in the Control Group.
(b) Liver Function Tests:
(i) Serum bilirubin, serum Alkaline phosphatase, serum Total protein/Al: Gl, SGOT and SGPT all reverted to normal or near normal in 73.68% of the Liv.52 treated cases within 12-24 months as against only 37.5% of cases of the Control Group within the same period.
(ii) B.S.P. Excretion studies done in a limited number of cases (5 Liv.52 and 5 Control) showed a much greater excretion in 4 out of 5 of the Liv.52 treated cases as against only 1 out of 5 of the Control cases.
Mukherjee and Das Gupta also reported a highly significant improvement in all the above parameters when the cases were treated with the drug for a minimum period of 9 months.
(iii) Protein Electrophoresis showed an increase in all the fractions of globulin in cirrhosis in all the cases with predominance of IgG, which came down to normal within 18-24 months in 73.68% of the cases of the Liv.52 Group against none in the Control Group, 5 of the 8 latter cases showing a further progressive increase in the component within the same period.
(c) Histopathological Studies: Four cases of the Liv.52 Group (as against none in the Control Group) showed a remarkable improvement in 12 months showing a normal liver architecture with minimal fibrosis, and remained so after another 24 months. Another 10 cases showed a fair degree of improvement in liver architecture with arrest of the progress of fibrosis, as against progressive fibrosis and further distortion of the liver architecture in most of the cases of the Control Group.
Mukherjee and Das Gupta, and others also reported more or less similar findings after prolonged treatment of their cases with Liv.52.
Considering the clinical, biochemical and histopathological parameters, the present study revealed “Fair to Good” results in 73.68% of the cases treated with Liv.52 as against only 37.5% of the cases in the Control Group.
A series of long-term experimental studies carried out by different workers substantiate the protective and regenerative action of Liv.52 on the liver against a battery of hepatotoxins (Murkibhavi and Sheth, 195714, Sheth et al, 196015, Joglekar et al16, Patel et al17, Karandikar et al18, 1963, Qazi, 196519, Captain and Syed,20 (1966); Joglekar and Leevy, 197021. Clinically also the drug has been tried extensively by different workers in various liver disorders and allied conditions, and by using different parameters of Liver Function Tests for assessment, as also by studying histopathological changes by serial liver biopsies. These workers have consistently confirmed that Liv.52 accelerates the clinical and biochemical recovery and also improves/arrests the progress of the histopathological changes (vide list of references). The present study adds strong support to and corroborates the findings of earlier workers. It may be said with confidence that in the absence of the availability of any better drug for the treatment of various liver disorders at the present moment, Liv.52 stands out on its own merit as a highly useful adjunct to the present-day therapeutic armamentarium against the ravages of the unfortunate diseases affecting the human liver.
SUMMARY AND CONCLUSIONS
A controlled study was undertaken to observe the efficacy of an indigenous drug Liv.52 introduced and marketed by The Himalaya Drug Co., Bombay on liver diseases. The present study covered a total of 104 cases of which 73 were treated with the above drug, 31 serving as Controls and belonged to the categories given below:
| Liv.52 | Control | ||
| (1) | Infective (Viral) Hepatitis | 30 | 15 |
| (2) | Chronic Active Hepatitis | 24 | 8 |
| (3) | Cirrhosis of the Liver | 19 | 8 |
The parameters chosen for assessment and analysis of the cases after follow-up of up to 3 years were (i) Clinical improvement, (ii) Improvement in the Biochemical profile, specially Liver Function Tests and (iii) Histopathological improvement (in the second and third categories).
On analysis of the data obtained after the full study, the results were graded as “Good”, “Fair” and “Poor” according to criteria already indicated in the text.
The following observations and conclusions were then arrived at:
Category (1) Infective Hepatitis: The results of treatment with Liv.52 were considered “Good” in 73.33%, “Fair” 23.33% and “Poor” in 3.33% of cases as against 26.66%, 66.66% and 6.66% respectively in the Control Group, both groups being analysed by the above parameters excepting histopathological studies which were not undertaken in this category of cases.
Category (2) Chronic Active Hepatitis: The results with Liv.52 were considered “Good” in 37.50%, “Fair” in 50.00% and “Poor” in 12.50% of cases as against 0%, 50% and 50% respectively in the Control Group analysed on the basis of all the three parameters.
Category (3) Cirrhosis of the Liver: The results with Liv.52 were considered as “Good” in 21.05% “Fair” in 52.63% and “Poor” in 26.32% of cases as against 0%, 37.5% and 62.5% respectively analysed by all the parameters of study.
No deleterious side effects were noted in any of the cases treated with the drug, even in those who failed to improve and in this respect the drug was considered absolutely safe.
In conclusion, it may be said with some confidence that since the studied categories of liver diseases which are so common in our country producing a significant degree of morbidity and mortality there being no “Specific” treatment for the conditions, the results of treatment with the indigenous drug Liv.52 appear highly encouraging, at least as a good palliative if not curative, to give the unfortunate sufferers an early improvement and a more prolonged, active and useful life. The drug may be considered as a significant advance, at least by one step, towards successful therapy of these chronic liver diseases.
ACKNOWLEDGEMENTS
We are grateful to the Principal-Superintendent, Medical College and Hospitals, Calcutta for kindly giving us permission to undertake the study and trials in the Medical College and Hospitals, Calcutta. Our sincere thanks also go to the teachers of the Department of medicine, M.C.H. who very graciously allowed us to include some of their cases in our study. We are also sincerely thankful to the Heads of the Biochemistry and Pathology Departments of the College for kindly helping us with the relevant investigations in their respective Departments. The supply of drugs was undertaken by The Himalaya Drug Co. without whose generous help the study would not have been possible, and our sincere thanks go to them. And last but not the least, we are immensely thankful to the patients who showed extreme co-operation and forbearance during the whole period of study.
REFERENCES
1. Sule, C.R., Pai, V.R., Damania, R.F. and Joshi, V.S. Studies with Liv.52 Therapy in Infective Hepatitis. J. Ind. med. Prof. (1968): 14, 6391.
2. Ramalingam, V., Sundaravalli, N. and Balagopal Raju, V. Liv.52 Studies in Acute Hepatitis. Ind. Paed. (1971): 12, 889.
3. Dave, D.S., Rajput, V.J. and Gupta, M.R. Clinico-Biochemical Study of Infective Hepatitis with Sepcial Reference to Liv.52 Therapy. Probe (1972): 4, 214.
4. Gupta, S., Khatri, R.L. and Srivastava, G. Therapuetic Effects of Liv.52 in Post-Necrotic Hepatitis. Probe (1972): 1, 15.
5. Ibid. Study of Infectious Hepatitis and Other Liver Disorders. Probe (1972): 2, 93.
6. Mukherjee, A.B. and Das Gupta, M. Treatment of Viral Hepatitis by an Indigenous Drug, Liv.52. Ind. Practit. (1970): 6,357.
7. Ibid. Chronic Active Hepatitis. J. Ind. med. Prof. (1971): 18, 8097.
8. Ibid. Cirrhosis of the Liver–results of treatment with an indigenous drug Liv.52 J. Ind. med. Prof. (1971): 17, 7853.
9. Prasad Lala Surajnandan and Prasad, K. Some observations on Liv.52 in the Treatment of Infective Hepatitis. Probe (1971): 3, 114.
10. Patel, G.T., Mruthyunjayanna, B.P., Seetharam, T.D. and Channe Gowda, A.C. Liv.52 Therapy in Viral Hepatitis. Probe (1972): 2, 112.
11. Mehrotra M.P. and Mathur, D.C. Liv.52 Trial in Infective Hepatitis. Antiseptic (1973): 2, 114.
12. Dayal, R.S., Kalra, K., Mital, V.P. and Sharan Rajiv, Liv.52 Therapy in cases of Malnutrition, Infective Hepatitis, Infantile Cirrhosis and Anorexia. Antiseptic (1974): 2, 89.
13. Cook, G.C. and Co-workers, Abstract of the proceedings of the fourth meeting of the International Association for the study of the liver. Gut. (1970): 2, 9.
14. Murkibhavi, G.R. and Sheth, U.K. Treatment of Jaundice in Dogs with an Indigenous Preparation Liv.52 (A Preliminary Report). Ind. Vet. J. (1957): 4, 276.
15. Sheth, S.C., Northover, B.J., Tibrewala, N.S., Warerkar, U.R. and Karande, V.S. Therapy of Cirrhosis of Liver and Liver Damage with Indigenous Durgs—Experimental and Clinical Studies, Ind. J. Ped. (1960): 149, 202.
16. Joglekar, G.V., Chitale, G.K. and Balwani, J.H. Protection by Indigenous Drugs against Hepatotoxic Effects of Carbon Tetrachloride in Mice. Acta Pharmacol et Toxicol (1963): 20, 73.
17. Patel, J.R. and Sadre, N.L. Effect of Liv.52 on Structural and Functional Damage caused by Hepatotoxic Agents. Probe (1963): 1, 19.
18. Karandikar, S.M., Joglekar, G.V., Chitale, G.K. and Balwani, J.H. Protection by Indigenous Drugs against Hepatotoxic Effects of Carbon Tetrachloride—“A long term study”. Acta Pharmacol et Toxicol (1963): 20, 274.
19. Kazi, I.H. Effect of Liv.52 on Biochemical and Functional Abnormalities of the Liver, Probe (1965): 5, 1.
20. Captain, S.R. and Syed, A.H. clinical Study on Liv.52 in Race Horses. Ind. Vet. J. (1966): 43, 11.
21. Joglekar, G.V. and Leevy, C.M. Effect of an Indigenous Drug on I.C.G. (Indocyanine Green): Clearance and Autoradiographic Pattern in Albino Rats with Experimentally Induced Hepatotoxicity. J. Ind. med. Prof. (1970): 12, 7480.
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