The efficacy of long-term intermittent administration of glycyrrhizin in HBe antigen-positive chronic active hepatitis K. Fujisawa, Y. Watanabe, H. Kawase, M. Zeniya, and H. Kameda First Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan Introduction Glycyrrhiza glabra is distributed widely throughout Asia, and its dried root, Glycyrrhizae radix of licorice root, has been used as a traditional drug in Eastern as well as in Western medicine, having anti-inflammatory, anti-allergic, and detoxicating effects. Its main effective component is one of the triterpenoid saponins, glycyrrhizin (glycyrrhetinic acid diglucur- onide; Fig 1). Stronger Neo-Minophagen C (SNMC)° is @ solution for- intravenous administration composed of glycyrrhizin (0.2%), glycine (2.0%), and cysteine (0.1%). In 1977 its therapeutic efficacy in cases of chronic active liver disease given 40 mL daily for one month was confirmed Japan by a randomized, double-blind, controlled trial; 133 cases were studied, 67 receiving SNMC and 66 a placebo.' ‘The general therapeutic usefulness ‘of SNMC was confirmed by the doctors in charge, with a clearly signifi- cant difference from the placebo group (p<0.001). Among the laboratory findings, marked improvements were observed in serum aminotransferase levels from the first week, and in y-GTP levels at the fourth week of medication in the SNMC group (Fig2).'* Improvement in serum aminotransferase levels seemed to play a major. role in the gencral usefulness rating in this trial. No side effects such as hypokalemia or hypertension were observed. However, rebound in the aminotransferase levels was observed after rapid discontinuation of the treatment. Accordingly, SNMC therapy is considered to be warranted in chronic active hepatitis with fluctuating, unsettled serum aminotransferase levels. . 17Fujisawa et ab : cH, coon Giycyrrhizin CathaOu 82g oul T Jeu, oF, ch, OCHCH, coor ©, 7 on . ‘coon on on Fig 1 Structural formula of glyeyerhizin, + Ue 12342468 r2342468 12342468 Time (weeks) ‘Time (weeks) ‘Time (weeks) Fig2 Effects of SNMC (40m iv for 4 weeks) on serum enzyme levels. Hatched area= period of administration. SNMC group; Placebo group. Methods and subjects As treatment of chronic active liver disease is genetally continued for at Teast one year to achieve clinical, biochemical, and histologic resolution, parenteral administration should be intermittent to minimize the inconve- nience to the patient. The efficacy of long-term intermittent administra tion of SNMC was therefore examined in our clinic in cases of HBeAg- positive chronic hepatitis. ‘Treatment was initiated with 40 mL of SNMC infused once every other day for several weeks and thereafter twice a week for a few months as maintenance treatment. Once serum aminotransferase levels had im- proved and stabilized, the frequency was further reduced to once'a week or every second week for withdrawal. Q 128Glyeyrihizin in HBeAg positive CAH Results, Eighteempatients with HBeAg-positive chronic hepatitis were thus treated with SNMC intermittently for 2.70.9 years, and their clinical courses were followed for 4.2-+1.4 years. They comprised 14 males and four females with an average age of 37.8:£7.1 years; 16 had chronic active and two chronic persistent hepatitis. ‘The initial average level of serum alanine aminotransferase (ALT) in these 18 cases (186-157 U/L) improved significantly to 81462 U/L after three months of therapy; the efficacy rate was 944%, The therapy had extensive influence on the functional features of the disease, and serum aminotransferase levels, y-GTP, profiles of serum proteins, and indo- HBeAg seroconverted Teases ais HBeAg-posiive Hea Girone hepatic 18eas Cow HBCAE cas HBeAg eae eases Fig3 Effects of long-term intermittent SNMC therapy on serum HBe antigen- antibody system, Table 1 Details of effects of intermitten hepatitis, 1 SNMC therapy on HBeAg-positive chronic Duration of the suc Followup Dui : NM ie Homor therapy uni ser- Fay No ch Aw Fsengranie SiMe Somesion or cares(8) (yx) HBeAa/ disappearance HiBe system therapy Orimeae Ca) Oo Results Wekg — CAH seroconverted _7(39.8%) 354461 49408 3.3407 12 408 Heap CAH este 4222) “8284 35407 25405 095403 cats Het GPU? sees 3541717409 16895) Total 18 378471 42414 — 2.7209 19