Jpn. J. Infect. Dis., 52, 1999

Laboratory and Epidemi010.gy Communications

Mitigation of Hepato‑Cellular Injury Caused by HAART with Glycyrrhizin
Compound in Patients Co‑Infected with HIV and HCVYoshihiko Yamamotol･2, Akira Yasuokal , Natsuo Tachikawal , Katsuji Teruyal , IkumiGenkal ,MasazumiYamaguchil, Chie Yasuokal, YoshimiKikuchil, Makoto Aokiland Shinichi Okal*]AIDS Clinical Center, International Medical Center of Japan,
7Toyama 1‑21 ‑1, Shinjuku, Tokyo 162‑8655 and2The Organization jTor Pharmaceutical SajTetyand Research of Japan,Kasumigaseki 3‑3‑2, Chiyoda, To砂0 1 0010013

Communicated by Hiroshi Yoshikura(Accepted January 5, 2000)

Hepato‑cellular Injury ∝Cumng SeVeralweeks after initia‑

all patients with HCV. Glycyrrhizin is reported to have ation of highly active anti‑retroviral therapy (HAART) against
HIV infection is not infrequent. In most cases, increase ofprotective effect on hepatocyte (3). SNMC consists of O･2%

serum alanine aminotransferase (Alュ) is transient and it

glycyrrhizin, 0. 1 % cysteine, and 2.0% glyclne in physiologlC
saline, and has been approved by the Ministry of Health anddecreases spontaneously without any treatment. However,Welfare of Japan in the treatment for chronic hepatitis･ Here

Some patients dually infected with HIV and hepatitis virus

we report a successful mitigation of HAART‑induced hepato‑

are obliged to discontinue HAART because of moderate orcellular lqury With SNMC without reduction or discontinua‑

severe hepato‑cellular injuries (I,2). In our hospital, 48 out

tion of any antトHIV drugs.

of 270 patients who had been recelVlng PrOteaSe inhibitors

Four hemophiliacs (cases 1‑4), dually infected with HIV

since 1 997 developed highserum All level (increase by moreand HCV, had mderate hepato‑cellular Injury after initiation

than three‑fold of basalvalues and/or morethan 200 IU/Lof HAART (stavudine, 1amivudine, and protease inhibitors).
TheirAIJ levels were mildly elevated txdore HAART, indicat‑【nomal range 0‑SO∃).

Incidence of the hepatitis C virus (HCV) infection isrelatively high in Japan; almost all Japanese HIV‑infected
hemophiliacs have tested positive for antibodies to HCVCurrently, a glycyrrhizin compound Stronger‑nco‑Minophagen

lng that they had chronic active hepatitis･ They had nausea

and general malaise, and showed further increase of All;
more than 280 to 480 IU/L within 5 weeks after initiationof HAART (case 2, 14 Weeks later). Cases land 3 had todiscontinue HAART as a result of hepato‑cellular Injury.

C (SNMC) is widely used to treat hepato‑cellular injury ind4T. 3TC andHARRT( ■｣ト)and SNMC (‑)
600

500

TOSYC
● ●● ■ 兩CーCase1 ･.●..Case2 ■コ‑Case3 ･.■.Case4400
SerurTIALT( lU/L)

300

200＼よ 犯R＼Lml.i.ド...i剪●●●ー ◆ ● ● ● ◆ ● ● ◆ ● ◆ 弼ER粐粫 粢 粐粐褪100)●｡ー ● ● ■■■■■■ 一一一■一l 停zB粐"rr苒穩穩ﾂr罎穩ﾓ｢粐粐r穩r苒苒霰20‑5M‑4M･‑3M‑1M‑2Ⅵrlw

0Iw

2W

3W

4W

5W

6W

7W

8W

4M

6M

Time course (week, month)Figure･ CIinicalcourse of patients･

d4T; stavudine, 3TC; 1amivudine, IDV; indinavir, RTV;ritonavir, SQV; saquinavir, NFV; nelfinavir*Co汀eSpOnding author: Fax: +81‑3‑5273‑5193, E‑mail: oka@

imcj.hosp.goJP248

Jpn. J. Infect. Dis., 52, 1999

cellular Injury after HAART can be caused by three possible
mechanis‑ms; side effects by HAART itself, exacerbation ofThese patients were then hospitalized and administered withSNMC intravenously, and HAART was reinitiated after we
had obtained infbmed consent.
Daily administration of SNMC was started withimitial dosesof 40 to 80 ml and gradually tapered with careful monitoringofAIJ. SNMC was administered for 16 to 46 days. Clinicalcomplaints disappeared from all of these patients within 10days, and serum ATL values immediately declined, reaching

HCV hepatitis,and transient loal immune response to HCV in
the course of immune reconstitution (4). The cause of thehepatDcellular Injury inthese four cases was unclear･ However,
the third mechanism is most likely because there were no

slgnificant increases of HCV viral load nor any slgnS Of
exacerbation of HCV hepatitis in any patients･ SNMC iscost‑effective and has a low toxicity. This limited pilot study

less than I(氾IU/Lwithin 4 weeks (Fig.).Asa consequence,

all of these patients were able to continue HAART without
reducing any anti‑HIV drugs. Although All of all patients

indicated that a larger clinical trial is warranted for cases

suffering from hepato‑cellular Injury aS a result of HAART･

did not stay within the normal limit, further elevation ofAIJ
was not obseⅣed up to 4 months after completion of SNMC.

This work was supported by grants fromthe Ministry ofNo side effects, such as the pseudo‑aldosteronism often

Health and Welfare of Japan, and the Organization of

induced by the glycy汀hizin (3) in SNMC, were obseⅣed.

Pharmaceutical Safety and Research (OPSR) of Japan･

Evaluation of HCV viral load showed no slgnificant changes
such as those obseⅣed in other HCV (+) / HIV (‑) patients.

REFERENCES

HIVl viral load was suppressed to less than 200 copies/ml
within 2 mqnths in cases 2, 3, and 4, and was decreased to

1. Matsuda, ∫., Gohchi, K. and Yamanaka, M. (1997):

4400‑2200copies/ml within 4 weeks in case 1 , indicatlng thatHIVl viral load was adequately suppressed in all clinical

Severe hepatitis in patients with AIDS and haemophilia

courses･ In addition,another hemophiliac patient who showed

B treated with indinavir. hncet, 350, 364.
2. Brau, N.,Leaf, H. L., WleCZOrek, R. L and Margolis, DI

persistent elevation in serum All for 5 months after discon‑

M. ( 1 997): Severe hepatitis in three AIDS patients treatedtinuation of previous HAART (AZT, ddC, and SQV), wasadministered with SNMC. His All had declined to 335‑61

3. van Rossum,T G.,Vulto,A. G., de Man, 良.A., Brouwer, ∫.

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T.and Schalm, S. W. (1998): Review article: glycyrrhizin

IU/L within 19 days, and he was able at that time to reinitiate
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remained lower than 96 IU/L fわr the followlng 6 months･

The precise action mechanism of SNMC is still unclear.
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4. John, M., Flexman, J. and French, M.A. (1998): Hepatitis

has been confirmed by many Japanese physicians throughinfected patients with protease inhibitors: an immune

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C vims‑associated hepatitis followlng treatment Of HIV‑249