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|Year : 1991 | Volume
| Issue : 3 | Page : 163-7
Ribavirin in acute viral hepatitis.
Tilve GH, Patel KC, Mogre VM
Department of Medicine, K. E. M. Hospital, Parel, Bombay, Maharashtra.
Department of Medicine, K. E. M. Hospital, Parel, Bombay, Maharashtra.
Sixty-four patients suffering from acute viral hepatitis (excluding those suffering from hepatitis B) were selected for the double blind clinical trial. They were randomly allocated to either ribavirin therapy (200 mg four times a day) or placebo. Four patients were lost to follow up and therefore final analysis was carried out on 60 patients (thirty had received ribavirin and the rest placebo). Patients receiving ribavirin showed significant rapid improvement, with the disappearance of annoying symptoms (e.g., nausea, vomiting, etc) and return of good appetite; moreover, the abnormal blood parameters showed significant rapid changes towards normal values in ribavirin treated patients as compared to those observed in placebo group. Ribavirin was well tolerated and there were no side effects. Since acute viral hepatitis is endemic with outbreaks of epidemics in many areas at various times and as yet there is no effective anti-viral drug available with the physicians in India, ribavirin is indeed a most welcome drug for its therapy.
|How to cite this article:|
Tilve G H, Patel K C, Mogre V M. Ribavirin in acute viral hepatitis. J Postgrad Med 1991;37:163
Viral hepatitis is a major public health problem, which occurs, in sporadic and endemic forms.
Ribavarin is a virustatic drug, which acts on both RNA and DNA viruses. It is a synthetic nucleoside analogue, structurally related to inosine and guanosine and has a broad spectrum of antiviral activity. It is used in patients suffering from infections due to respiratory syncytial virus (RSV), influenza virus A, herpes virus, measles and lassa fever. Since it is phosphorylated in liver where it accumulates, ribavarin might be expected to be useful in treating viral hepatitis.
Sidwell et al have demonstrated usefulness of ribavarin in experimental model of murine hepatitis. A marked reduction in hepatic inflammation and necrosis along with decrease in serum bilirubin and enzymes was observed in these mice. Ribavarin also showed encouraging results in a clinical trial conducted at Poona in patients with infective hepatitis.
In view of these data, we decided to evaluate efficacy of ribavarin in acute viral hepatitis.
The study was carried out on 64 patients who attended King Edward Memorial Hospital, Parel, Mumbai. The first 4 patients were treated in the wards; subsequently the rest were treated as out-patients from April, 1989 to November, 1989. Diagnosis of acute viral hepatitis was made from careful history and clinical examination coupled with laboratory investigations. Children, pregnant or lactating women and persons with complications like encephalopathy were not included in this trial.
Other exclusion criteria were positive Australia antigen titres, evidence of chronic liver disease, amoebic hepatitis, malignancy, red blood cell dyscrasias and renal failure (creatinine < 2.5 mg/100 ml), history of drug addiction, alcoholism and history of receiving gamma globulin injection in the recent past.
Informed written consent was obtained from each patient prior to entering the trial. Thereafter, the patient was randomly allocated to either Group A or Group B for therapy. Patients received one capsule 4 times a day either from pack A or pack B in the respective groups for 14 days. Neither the investigator nor the patients knew the drugs contained in pack A or pack B, hence the double blind design of the trial was maintained.
Laboratory investigations included haemoglobin, white blood cell count, blood urea nitrogen, alkaline phosphatase, total and direct bilirubin, SGOT and SGPT; and were done before the start of the trial (on the 1st day) and then on the 5th, 10th and 14th days. Repeated clinical examinations were done to follow the degree of icterus and the extent palpable liver. Patients were also closely monitored to detect the appearance of any side effects. Statistical Analysis was carried out using the Wilcoxan test.
Out of the 64 patients entering the trial, 4 did not return for regular follow-up and hence they were considered as lost to follow-up and not included in the final analysis. The trial report therefore refers to 60 patients who completed the trial as per the protocol. After completion of the study the medication assignment code was broken and it was found that patients in Group A had received ribavarin while those in Group B had received placebo. Each capsule from pack A contained ribavarin 200 mg and the dose of ribavarin used in this study was 200 mg four times a day. Group A and B included patients matching in age, sex and hepatic dysfunction parameters. A comparison of significant biochemical values during the treatment has been given in detail in [Table - 1] and (See [Figure:1], [Figure:2], [Figure:3] & [Figure:4] mean reductions in the total and direct bilirubin values along with SGOT and SGPT were significantly more in of the ribavarin group as compared to placebo group on the 5th, 10th and 14th days of treatment. More rapid reduction in all these parameters occurred in the ribavarin treated patients from the 5th of treatment till the 14th day. This was associated with increased appetite, attainment of afebrile state and increased sense of well-being.
In addition, as shown in [Table - 2], number of patients attaining normal values of hepatic dysfunction parameters, viz., bilirubin - total and direct, SGOT and SGPT on 14th day were significantly more in ribavarin treated group as compared to placebo group. No side effects were noticed in patients treated with ribavarin.
Hepatitis epidemic usually occurs due to contaminated water supply. After contracting hepatitis, but for supportive therapy a physician can do nothing. The need for a drug, which could help speedy recovery and therefore reduce the morbidity associated with this disease, has been keenly felt. The drug ribavarin is already marketed in western countries and has been shown to hasten the recovery from acute viral hepatitis.
Our double blind placebo controlled study with ribavarin was therefore initiated to evaluate the therapeutic potential of the drug in the treatment of acute hepatitis in Indian patients. Most of the patients from our study group had mild or moderate hepatitis. The study revealed that when scrum bilirubin and enzymes were used as criteria for assessment, there was an overall improvement with passage of time in all patients. However, the patients treated with ribavarin had a remarkably faster recovery (within 14 days) in terms of clinical and laboratory parameters as compared to patients receiving placebo. The difference between the treatments was found to be significant when statistical tests were applied. While producing this beneficial effect, ribavarin, in the dosage of 200 mg four times a day for fourteen days was not seen to be associated with any side effects.
We thank Lupin Laboratories Ltd., Bombay, for the liberal supply of the drugs and the financial assistance. We thank Dean, King Edward Memorial Hospital for allowing us to conduct the studies in our hospital.
Kastrup EK. In: “Drugs, Facts and Comparisons”. St. Luis: Division of JB Lippincott Co; 1989, pp 1615-1616. |
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