Evaluation of efficacy and safety of Liv.52 DS tablets in acute viral hepatitis:
A prospective, double-blind, randomized, placebo-controlled,
phase III clinical trial

Dr. Rajiv Baijal, M.D., D.N.B.1, Dr. Nikhil Patel, M.D.,2 and Dr. S. A. Kolhapure, M.D.3*
1Gastroenterologist, 2Research Associates, Department of Gastroenterology,
Jagjivanram Western Railway Hospital, Mumbai Central, Mumbai, India. 3Senior Medical Advisor, R&D Center, The Himalaya Drug Company, Bangalore, India

ABSTRACT Viral hepatitis (A, B, C, D, E and G) is a global public health problem, which is responsible for a major chunk of morbidity and mortality. Viral hepatitis occurs endemically and sporadically throughout the world, depending on the endemicity of infection. The primary goal in the management of acute viral hepatitis is early renormalization of hepatic functions with symptomatic and clinical recovery. This study was planned to evaluate the efficacy and safety of Liv.52 DS tablets in acute viral hepatitis. This study was a prospective, double-blind, randomized, placebo-controlled, phase III clinical trial conducted as per the Declaration of Helsinki, with strict adherence with the GCP ethical guidelines and was approved by the institutional ethics committee. A total of 50 patients with diagnosis of symptomatic acute viral hepatitis, and who were willing to give informed consent were included in the study. Pregnant women, patients with chronic hepatitis, patients with malignant jaundice, patients with other causes for acute hepatitis, and those who were unwilling to give informed consent were excluded from the study. At the initial visit, informed written consent was obtained from all the enrolled patients, and randomization and double blinding was done. A detailed medical history was obtained from all the enrolled patients, which was followed by thorough clinical examination. All patients were subjected to hematological and biochemical investigations, which included CBC, LFTs, ESR and tests for viral markers (IgM antiHAV, IgM antiHBc, HBsAg, IgM antiHEV). The drug group received Liv.52 DS and the other group received placebo, in a dose of 2 tablets two times-a-day, orally, for 4 months. Patients were not allowed to take any other medication, which would have any significant effect on LFT. All patients were followed up every month for a period of 4 months. At each follow-up visit, the investigator recorded any information about adverse events, and a symptomatic evaluation was conducted, which was followed by thorough clinical examination. The subjective symptomatic improvement was assessed on a predefined 0 to 3 score scale. At the end of 4 months, changes in the hematological and biochemical

ABBREVIATIONS ALP : Alkaline phosphatase ALT : Alanine aminotransferase AST : Aspartate aminotransferase CBC : Complete blood count CCl4 : Carbon tetrachloride DLC : Differential leucocyte count DNA : Deoxyribonucleic acid ESR : Erythrocyte sedimentation rate ET : NANBH : Enterically transmitted non-A non-B hepatitis GCP : Good clinical practice HA : Hepatitis A HAV : Hepatitis A virus Hb : Hemoglobin HBC : Hepatitis B core (antigen) HBeAg : Hepatitis Be antigen HBsAg : Hepatitis B surface antigen HBV : Hepatitis B virus HCV : Hepatitis C virus HDV : Hepatitis D virus HEV : Hepatitis E virus HGBV-C/ GB-C : Hepatitis GB virus-C HGV : Hepatitis G virus IgG : Immunoglobulin G IgM : Immunoglobulin M LFT : Liver function test PC : Platelet count RNA : Ribonucleic acid SA : Serum albumin SB : Serum bilirubin SG : Serum glutathione SGOT : Serum glutamic oxaloacetic transaminase SGPT : Serum glutamic pyruvic transaminase TB : Total bilirubin TLC : Total leucocyte count TP : Total protein WBC : White blood cells

parameters from baseline values to the values at the end of the study, the duration of recovery, incidence of adverse events and patient compliance to the drug treatment were recorded. All adverse events either reported or observed by patients were recorded with information about severity, duration and action taken regarding the study drug. The predefined primary efficacy endpoints were rapid symptomatic improvement, renormalization of hematological and biochemical parameters, and total duration of clinical recovery. The predefined secondary safety endpoints were incidence of adverse events during the study period and overall compliance to the drug treatment. Statistical analysis was done according to intention-to-treat principles. The minimum level of significance was fixed at 99% confidence limit and a 2-sided p value of <0.001 was considered significant.

A total of 50 patients were enrolled in the trial. The demographic and clinical profile, hematological and biochemical profile were similar in Liv.52 DS and placebo groups and the patients were equally distributed in both the study arms. The mean age of the enrolled patients was 33.42 years. The common symptoms reported by patients were jaundice, anorexia, nausea, vomiting, fever and pruritus. The common clinical findings were icterus and hepatomegaly. Laboratory investigations confirmed that 74% patients were suffering from hepatitis E, 10% from hepatitis B, 8% from hepatitis A, and 8% from hepatitis non A-E. There was a highly significant (p < 0.0001) and rapid symptomatic improvement in the mean scores for loss of appetite, weight loss, fatigue and jaundice in Liv.52 DS group, as compared to the placebo. There was a significant renormalization of the biochemical parameters of liver functions, after 2 months in Liv.52 DS group and after 3 months in the placebo group. There was a highly significant ( p < 0.0001) improvement in the blood proteins, and the levels of SA, SG and TP were renormalized. The increased level of ESR and WBC were significantly (p < 0.0001) reduced in Liv.52 DS group, as compared to the placebo group, at the end of the study. There were no clinically significant (p < 0.0001) changes in other biochemical parameters such as Hb levels and PC. There were no clinically significant adverse effects during the entire study period and the overall compliance to the drug treatment was excellent.

Therefore, it may be concluded that, Liv.52 DS tablets are clinically effective and safe in the management of acute viral hepatitis.


Refference: http://www.himalayahealthcare.com/pdf_files/liv250.pdf